Erik Van der Burg
Full Text Available BACKGROUND: A prevailing view is that audiovisual integration requires temporally coincident signals. However, a recent study failed to find any evidence for audiovisual integration in visual search even when using synchronized audiovisual events. An important question is what information is critical to observe audiovisual integration. METHODOLOGY/PRINCIPAL FINDINGS: Here we demonstrate that temporal coincidence (i.e., synchrony of auditory and visual components can trigger audiovisual interaction in cluttered displays and consequently produce very fast and efficient target identification. In visual search experiments, subjects found a modulating visual target vastly more efficiently when it was paired with a synchronous auditory signal. By manipulating the kind of temporal modulation (sine wave vs. square wave vs. difference wave; harmonic sine-wave synthesis; gradient of onset/offset ramps we show that abrupt visual events are required for this search efficiency to occur, and that sinusoidal audiovisual modulations do not support efficient search. CONCLUSIONS/SIGNIFICANCE: Thus, audiovisual temporal alignment will only lead to benefits in visual search if the changes in the component signals are both synchronized and transient. We propose that transient signals are necessary in synchrony-driven binding to avoid spurious interactions with unrelated signals when these occur close together in time.
van den Burg, E.; Cass, J.R.; Olivers, C.N.L.; Theeuwes, J.; Alais, D
Background: A prevailing view is that audiovisual integration requires temporally coincident signals. However, a recent study failed to find any evidence for audiovisual integration in visual search even when using synchronized audiovisual events. An important question is what information is
Kunert, R.; Jongman, S.R.
Many natural auditory signals, including music and language, change periodically. The effect of such auditory rhythms on the brain is unclear however. One widely held view, dynamic attending theory, proposes that the attentional system entrains to the rhythm and increases attention at moments of
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 developed...
Kunert, Richard; Jongman, Suzanne R
Many natural auditory signals, including music and language, change periodically. The effect of such auditory rhythms on the brain is unclear however. One widely held view, dynamic attending theory, proposes that the attentional system entrains to the rhythm and increases attention at moments of rhythmic salience. In support, 2 experiments reported here show reduced response times to visual letter strings shown at auditory rhythm peaks, compared with rhythm troughs. However, we argue that an account invoking the entrainment of general attention should further predict rhythm entrainment to also influence memory for visual stimuli. In 2 pseudoword memory experiments we find evidence against this prediction. Whether a pseudoword is shown during an auditory rhythm peak or not is irrelevant for its later recognition memory in silence. Other attention manipulations, dividing attention and focusing attention, did result in a memory effect. This raises doubts about the suggested attentional nature of rhythm entrainment. We interpret our findings as support for auditory rhythm perception being based on auditory-motor entrainment, not general attention entrainment. (PsycINFO Database Record (c) 2017 APA, all rights reserved).
Schneider, David M; Mooney, Richard
In the auditory system, corollary discharge signals are theorized to facilitate normal hearing and the learning of acoustic behaviors, including speech and music. Despite clear evidence of corollary discharge signals in the auditory cortex and their presumed importance for hearing and auditory-guided motor learning, the circuitry and function of corollary discharge signals in the auditory cortex are not well described. In this review, we focus on recent developments in the mouse and songbird that provide insights into the circuitry that transmits corollary discharge signals to the auditory system and the function of these signals in the context of hearing and vocal learning. Copyright © 2015 Elsevier Ltd. All rights reserved.
Prather, Jonathan F
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. This article is part of a Special Issue entitled "Communication Sounds and the Brain: New Directions and Perspectives". Copyright © 2013
Jepsen, Morten Løve; Ewert, Stephan D.; Dau, Torsten
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...
Jimenez-Fernandez, Angel; Cerezuela-Escudero, Elena; Miro-Amarante, Lourdes; Dominguez-Moralse, Manuel Jesus; de Asis Gomez-Rodriguez, Francisco; Linares-Barranco, Alejandro; Jimenez-Moreno, Gabriel
This paper presents a new architecture, design flow, and field-programmable gate array (FPGA) implementation analysis of a neuromorphic binaural auditory sensor, designed completely in the spike domain. Unlike digital cochleae that decompose audio signals using classical digital signal processing techniques, the model presented in this paper processes information directly encoded as spikes using pulse frequency modulation and provides a set of frequency-decomposed audio information using an address-event representation interface. In this case, a systematic approach to design led to a generic process for building, tuning, and implementing audio frequency decomposers with different features, facilitating synthesis with custom features. This allows researchers to implement their own parameterized neuromorphic auditory systems in a low-cost FPGA in order to study the audio processing and learning activity that takes place in the brain. In this paper, we present a 64-channel binaural neuromorphic auditory system implemented in a Virtex-5 FPGA using a commercial development board. The system was excited with a diverse set of audio signals in order to analyze its response and characterize its features. The neuromorphic auditory system response times and frequencies are reported. The experimental results of the proposed system implementation with 64-channel stereo are: a frequency range between 9.6 Hz and 14.6 kHz (adjustable), a maximum output event rate of 2.19 Mevents/s, a power consumption of 29.7 mW, the slices requirements of 11141, and a system clock frequency of 27 MHz.
Hironori Kuga, M.D.
We acquired BOLD responses elicited by click trains of 20, 30, 40 and 80-Hz frequencies from 15 patients with acute episode schizophrenia (AESZ, 14 symptom-severity-matched patients with non-acute episode schizophrenia (NASZ, and 24 healthy controls (HC, assessed via a standard general linear-model-based analysis. The AESZ group showed significantly increased ASSR-BOLD signals to 80-Hz stimuli in the left auditory cortex compared with the HC and NASZ groups. In addition, enhanced 80-Hz ASSR-BOLD signals were associated with more severe auditory hallucination experiences in AESZ participants. The present results indicate that neural over activation occurs during 80-Hz auditory stimulation of the left auditory cortex in individuals with acute state schizophrenia. Given the possible association between abnormal gamma activity and increased glutamate levels, our data may reflect glutamate toxicity in the auditory cortex in the acute state of schizophrenia, which might lead to progressive changes in the left transverse temporal gyrus.
Full Text Available Information received from different sensory modalities profoundly influences human perception. For example, changes in the auditory flutter rate induce changes in the apparent flicker rate of a flashing light (Shipley, 1964. In the present study, we investigated whether auditory information would affect the perceived offset position of a moving object. In Experiment 1, a visual object moved toward the center of the computer screen and disappeared abruptly. A transient auditory signal was presented at different times relative to the moment when the object disappeared. The results showed that if the auditory signal was presented before the abrupt offset of the moving object, the perceived final position was shifted backward, implying that the perceived offset position was affected by the transient auditory information. In Experiment 2, we presented the transient auditory signal to either the left or the right ear. The results showed that the perceived offset shifted backward more strongly when the auditory signal was presented to the same side from which the moving object originated. In Experiment 3, we found that the perceived timing of the visual offset was not affected by the spatial relation between the auditory signal and the visual offset. The present results are interpreted as indicating that an auditory signal may influence the offset position of a moving object through both spatial and temporal processes.
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.
Mittal, Rahul; Debs, Luca H; Nguyen, Desiree; Patel, Amit P; Grati, M'hamed; Mittal, Jeenu; Yan, Denise; Eshraghi, Adrien A; Liu, Xue Zhong
Ear is a sensitive organ involved in hearing and balance function. The complex signaling network in the auditory system plays a crucial role in maintaining normal physiological function of the ear. The inner ear comprises a variety of host signaling pathways working in synergy to deliver clear sensory messages. Any disruption, as minor as it can be, has the potential to affect this finely tuned system with temporary or permanent sequelae including vestibular deficits and hearing loss. Mutations linked to auditory symptoms, whether inherited or acquired, are being actively researched for ways to reverse, silence, or suppress them. In this article, we discuss recent advancements in understanding the pathways involved in auditory system signaling, from hair cell development through transmission to cortical centers. Our review discusses Notch and Wnt signaling, cell to cell communication through connexin and pannexin channels, and the detrimental effects of reactive oxygen species on the auditory system. There has been an increased interest in the auditory community to explore the signaling system in the ear for hair cell regeneration. Understanding signaling pathways in the auditory system will pave the way for the novel avenues to regenerate sensory hair cells and restore hearing function. J. Cell. Physiol. 232: 2710-2721, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
Favrot, Sylvain Emmanuel; Buchholz, Jörg
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....
Møller, Ian M; Sweetlove, Lee J
Reactive oxygen species (ROS) production 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 might induce a general stress response, but it does not ha...... and regulate source-specific genes and in this way contribute to retrograde ROS signalling during oxidative stress. Likewise, unmodified peptides deriving from the breakdown of redundant proteins could help coordinate organellar and nuclear gene expression......Reactive oxygen species (ROS) production 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 might induce a general stress response, but it does not have...... the required specificity to selectively regulate nuclear genes required for dealing with localized stress, e.g. in chloroplasts or mitochondria. Here we argue that peptides deriving from proteolytic breakdown of oxidatively damaged proteins have the requisite specificity to act as secondary ROS messengers...
Tjan, Bosco S; Chao, Ewen; Bernstein, Lynne E
Acoustic speech is easier to detect in noise when the talker can be seen. This finding could be explained by integration of multisensory inputs or refinement of auditory processing from visual guidance. In two experiments, we studied two-interval forced-choice detection of an auditory 'ba' in acoustic noise, paired with various visual and tactile stimuli that were identically presented in the two observation intervals. Detection thresholds were reduced under the multisensory conditions vs. the auditory-only condition, even though the visual and/or tactile stimuli alone could not inform the correct response. Results were analysed relative to an ideal observer for which intrinsic (internal) noise and efficiency were independent contributors to detection sensitivity. Across experiments, intrinsic noise was unaffected by the multisensory stimuli, arguing against the merging (integrating) of multisensory inputs into a unitary speech signal, but sampling efficiency was increased to varying degrees, supporting refinement of knowledge about the auditory stimulus. The steepness of the psychometric functions decreased with increasing sampling efficiency, suggesting that the 'task-irrelevant' visual and tactile stimuli reduced uncertainty about the acoustic signal. Visible speech was not superior for enhancing auditory speech detection. Our results reject multisensory neuronal integration and speech-specific neural processing as explanations for the enhanced auditory speech detection under noisy conditions. Instead, they support a more rudimentary form of multisensory interaction: the otherwise task-irrelevant sensory systems inform the auditory system about when to listen. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
Van der Burg, Erik; Olivers, Christian N. L.; Bronkhorst, Adelbert W.; Theeuwes, Jan
Searching for an object within a cluttered, continuously changing environment can be a very time-consuming process. The authors show that a simple auditory pip drastically decreases search times for a synchronized visual object that is normally very difficult to find. This effect occurs even though the pip contains no information on the location…
The phenomenon of crossmodal dynamic visual capture occurs when the direction of motion of a visual cue causes a weakening or reversal of the perceived direction of motion of a concurrently presented auditory stimulus. It is known that there is a perceptual bias towards looming compared to receding stimuli, and faster bimodal reaction times have recently been observed for looming cues compared to receding cues (Cappe et al., 2009). The current studies aimed to test whether visual looming cues are associated with greater dynamic capture of auditory motion in depth compared to receding signals. Participants judged the direction of an auditory motion cue presented with a visual looming cue (expanding disk), a visual receding cue (contracting disk), or visual stationary cue (static disk). Visual cues were presented either simultaneously with the auditory cue, or after 500 ms. We found increased levels of interference with looming visual cues compared to receding visual cues, compared to asynchronous presentation or stationary visual cues. The results could not be explained by the weaker subjective strength of the receding auditory stimulus, as in Experiment 2 the looming and receding auditory cues were matched for perceived strength. These results show that dynamic visual capture of auditory motion in the depth plane is modulated by an adaptive bias for looming compared to receding visual cues.
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.
Petocz, Agnes; Keller, Peter E; Stevens, Catherine J
In auditory warning design the idea of the strength of the association between sound and referent has been pivotal. Research has proceeded via constructing classification systems of signal-referent associations and then testing predictions about ease of learning of different levels of signal-referent relation strength across and within different types of auditory signal (viz., speech, abstract sounds, and auditory icons). However, progress is hampered by terminological confusions and by neglect of the cognitive contribution (viz., learning) of the person or user. Drawing upon semiotics and cognitive psychology, the authors highlight the indexical (as opposed to iconic) nature of so-called auditory icons, and the authors identify the cogniser as an indispensable element in the tripartite nature of signification. Classifications that neglect this third element, defining signal-referent relation strength only dyadically, yield results confounded by learning; classifications that correctly include the triadic relation yield research predictions that are redundant. These limitations of the standard method of constructing and testing classification systems suggest that auditory warning design must take the cognitive contribution of the user into account at an earlier stage in the design process. (c) 2008 APA, all rights reserved
Chi, Chia-Fen; Dewi, Ratna Sari; Huang, Min-Hua
Twenty-one experienced drivers were recruited for the evaluation of sounds of four functions (horn, indicator, door open warning, and parking sensor) made by 11 car brand names. Each participant was required to evaluate all of the above sound signals by a pair-comparison test. After the comparison test, each participant was shown his/her pair-comparison result and was asked to comment on their preference and appropriateness of a sound. The physical properties and interview data were compared and summarized to propose design recommendations. Our results indicate that complex tones and a fundamental frequency between 500 and 1000 Hz were most preferred for horns while for indicators the preferred sounds had a higher dominant frequency. To reduce monotony, the indicators with double clicks and an OFF time interval of between 330 and 400 ms between two clicks were most preferred. Regarding door warning sounds, the waveform starting with a higher intensity then fading towards zero intensity is most preferred while for parking sensors, sounds beginning with a longer OFF time (about 500 ms) and having 3 or 4 distinctive tempo variations were most preferred. The relationship between pleasurability and pitch, loudness, and the tempo of sound signals basically followed an inverted-U function. Sound designers should avoid using very extreme parameter values when generating sound for a given function. Copyright Â© 2016 Elsevier Ltd. All rights reserved.
Chan, Jason S; Spence, Charles
In auditory research, it is often desirable to present more than two auditory stimuli at any one time. Although the technology has been available for some time, the majority of researchers have not utilized it. This article provides a simple means of presenting multiple, concurrent, independent auditory events, using two or more different sound cards installed within a single computer. By enabling the presentation of more auditory events, we can hope to gain a better understanding of the cognitive and attentional processes operating under more complex and realistic scenes, such as that embodied by the cocktail party effect. The software requirements are Windows 98SR2/Me/NT4/2000/XP, Visual Basic 6.0, and DirectX 7.0 or above. The hardware requirements are a Pentium II, 128 MB RAM, and two or more different sound cards.
Elliott, Taffeta M; Christensen-Dalsgaard, Jakob; Kelley, Darcy B
of the rate of clicks in calls. The majority of neurons (85%) were selective for click rates, and this selectivity remained unchanged over sound levels 10 to 20 dB above threshold. Selective neurons give phasic, tonic, or adapting responses to tone bursts and click trains. Some algorithms that could compute...... of auditory neurons in the laminar nucleus of the torus semicircularis (TS) of X. laevis specializes in encoding vocalization click rates. We recorded single TS units while pure tones, natural calls, and synthetic clicks were presented directly to the tympanum via a vibration-stimulation probe. Synthesized...... click rates ranged from 4 to 50 Hz, the rate at which the clicks begin to overlap. Frequency selectivity and temporal processing were characterized using response-intensity curves, temporal-discharge patterns, and autocorrelations of reduplicated responses to click trains. Characteristic frequencies...
Baltzell, Lucas S; Billings, Curtis J
The purpose of this study was to determine the effects of SNR and signal level on the offset response of the cortical auditory evoked potential (CAEP). Successful listening often depends on how well the auditory system can extract target signals from competing background noise. Both signal onsets and offsets are encoded neurally and contribute to successful listening in noise. Neural onset responses to signals in noise demonstrate a strong sensitivity to signal-to-noise ratio (SNR) rather than signal level; however, the sensitivity of neural offset responses to these cues is not known. We analyzed the offset response from two previously published datasets for which only the onset response was reported. For both datasets, CAEPs were recorded from young normal-hearing adults in response to a 1000-Hz tone. For the first dataset, tones were presented at seven different signal levels without background noise, while the second dataset varied both signal level and SNR. Offset responses demonstrated sensitivity to absolute signal level in quiet, SNR, and to absolute signal level in noise. Offset sensitivity to signal level when presented in noise contrasts with previously published onset results. This sensitivity suggests a potential clinical measure of cortical encoding of signal level in noise.
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.
Vishakha W Rawool
Full Text Available Context: The ability to detect important auditory signals while performing visual tasks may be further compounded by background chatter. Thus, it is important to know how task performance may interact with background chatter to hinder signal detection. Aim: To examine any interactive effects of speech spectrum noise and task performance on the ability to detect signals. Settings and Design: The setting was a sound-treated booth. A repeated measures design was used. Materials and Methods: Auditory thresholds of 20 normal adults were determined at 0.5, 1, 2 and 4 kHz in the following conditions presented in a random order: (1 quiet with attention; (2 quiet with a visuo-spatial task or puzzle (distraction; (3 noise with attention and (4 noise with task. Statistical Analysis: Multivariate analyses of variance (MANOVA with three repeated factors (quiet versus noise, visuo-spatial task versus no task, signal frequency. Results: MANOVA revealed significant main effects for noise and signal frequency and significant noise–frequency and task–frequency interactions. Distraction caused by performing the task worsened the thresholds for tones presented at the beginning of the experiment and had no effect on tones presented in the middle. At the end of the experiment, thresholds (4 kHz were better while performing the task than those obtained without performing the task. These effects were similar across the quiet and noise conditions. Conclusion: Detection of auditory signals is difficult at the beginning of a distracting visuo-spatial task but over time, task learning and auditory training effects can nullify the effect of distraction and may improve detection of high frequency sounds.
... Federal Railroad Administration 49 CFR Part 233 RIN 2130-AC44 Signal System Reporting Requirements AGENCY... regulatory requirement that each carrier must file with FRA a signal system status report every five years... Reporting Requirements by updating an outdated statutory citation. DATES: Written comments must be received...
Li, Jingcheng; Liao, Xiang; Zhang, Jianxiong; Wang, Meng; Yang, Nian; Zhang, Jun; Lv, Guanghui; Li, Haohong; Lu, Jian; Ding, Ran; Li, Xingyi; Guang, Yu; Yang, Zhiqi; Qin, Han; Jin, Wenjun; Zhang, Kuan; He, Chao; Jia, Hongbo; Zeng, Shaoqun; Hu, Zhian; Nelken, Israel; Chen, Xiaowei
The ability of the brain to predict future events based on the pattern of recent sensory experience is critical for guiding animal's behavior. Neocortical circuits for ongoing processing of sensory stimuli are extensively studied, but their contributions to the anticipation of upcoming sensory stimuli remain less understood. We, therefore, used in vivo cellular imaging and fiber photometry to record mouse primary auditory cortex to elucidate its role in processing anticipated stimulation. We found neuronal ensembles in layers 2/3, 4, and 5 which were activated in relationship to anticipated sound events following rhythmic stimulation. These neuronal activities correlated with the occurrence of anticipatory motor responses in an auditory learning task. Optogenetic manipulation experiments revealed an essential role of such neuronal activities in producing the anticipatory behavior. These results strongly suggest that the neural circuits of primary sensory cortex are critical for coding predictive information and transforming it into anticipatory motor behavior. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: firstname.lastname@example.org.
Bowen, Amanda L; Ramachandran, Ramnarayan; Muday, Jeffrey A; Schirillo, James A
In the psychophysical phenomenon visual bias, an accurately localized irrelevant signal, such as a light, impairs localization of a spatially discrepant target, such as a sound, when the two stimuli are perceived as unified. Many studies have demonstrated visual bias in azimuth, but none have tested directly or found this effect in depth. The current study was able to produce over 90% bias in azimuth and somewhat less (83%) bias in depth. A maximum likelihood estimate can predict bias by the variance in the localization of each unimodal signal in each dimension in space.
Ghosh, Prasanta Kumar; Goldstein, Louis M; Narayanan, Shrikanth S
Understanding how the human speech production system is related to the human auditory system has been a perennial subject of inquiry. To investigate the production-perception link, in this paper, a computational analysis has been performed using the articulatory movement data obtained during speech production with concurrently recorded acoustic speech signals from multiple subjects in three different languages: English, Cantonese, and Georgian. The form of articulatory gestures during speech production varies across languages, and this variation is considered to be reflected in the articulatory position and kinematics. The auditory processing of the acoustic speech signal is modeled by a parametric representation of the cochlear filterbank which allows for realizing various candidate filterbank structures by changing the parameter value. Using mathematical communication theory, it is found that the uncertainty about the articulatory gestures in each language is maximally reduced when the acoustic speech signal is represented using the output of a filterbank similar to the empirically established cochlear filterbank in the human auditory system. Possible interpretations of this finding are discussed. © 2011 Acoustical Society of America
Kwon, Bomjun J
This article introduces AUX (AUditory syntaX), a scripting syntax specifically designed to describe auditory signals and processing, to the members of the behavioral research community. The syntax is based on descriptive function names and intuitive operators suitable for researchers and students without substantial training in programming, who wish to generate and examine sound signals using a written script. In this article, the essence of AUX is discussed and practical examples of AUX scripts specifying various signals are illustrated. Additionally, two accompanying Windows-based programs and development libraries are described. AUX Viewer is a program that generates, visualizes, and plays sounds specified in AUX. AUX Viewer can also be used for class demonstrations or presentations. Another program, Psycon, allows a wide range of sound signals to be used as stimuli in common psychophysical testing paradigms, such as the adaptive procedure, the method of constant stimuli, and the method of adjustment. AUX Library is also provided, so that researchers can develop their own programs utilizing AUX. The philosophical basis of AUX is to separate signal generation from the user interface needed for experiments. AUX scripts are portable and reusable; they can be shared by other researchers, regardless of differences in actual AUX-based programs, and reused for future experiments. In short, the use of AUX can be potentially beneficial to all members of the research community-both those with programming backgrounds and those without.
Teschner, Magnus J; Seybold, Bryan A; Malone, Brian J; Hüning, Jana; Schreiner, Christoph E
The neural mechanisms that support the robust processing of acoustic signals in the presence of background noise in the auditory system remain largely unresolved. Psychophysical experiments have shown that signal detection is influenced by the signal-to-noise ratio (SNR) and the overall stimulus level, but this relationship has not been fully characterized. We evaluated the neural representation of frequency in rat primary auditory cortex by constructing tonal frequency response areas (FRAs) in primary auditory cortex for different SNRs, tone levels, and noise levels. We show that response strength and selectivity for frequency and sound level depend on interactions between SNRs and tone levels. At low SNRs, jointly increasing the tone and noise levels reduced firing rates and narrowed FRA bandwidths; at higher SNRs, however, increasing the tone and noise levels increased firing rates and expanded bandwidths, as is usually seen for FRAs obtained without background noise. These changes in frequency and intensity tuning decreased tone level and tone frequency discriminability at low SNRs. By contrast, neither response onset latencies nor noise-driven steady-state firing rates meaningfully interacted with SNRs or overall sound levels. Speech detection performance in humans was also shown to depend on the interaction between overall sound level and SNR. Together, these results indicate that signal processing difficulties imposed by high noise levels are quite general and suggest that the neurophysiological changes we see for simple sounds generalize to more complex stimuli. Effective processing of sounds in background noise is an important feature of the mammalian auditory system and a necessary feature for successful hearing in many listening conditions. Even mild hearing loss strongly affects this ability in humans, seriously degrading the ability to communicate. The mechanisms involved in achieving high performance in background noise are not well understood. We
Moors, Pieter; Huygelier, Hanne; Wagemans, Johan; de-Wit, Lee; van Ee, Raymond
Previous studies using binocular rivalry have shown that signals in a modality other than the visual can bias dominance durations depending on their congruency with the rivaling stimuli. More recently, studies using continuous flash suppression (CFS) have reported that multisensory integration influences how long visual stimuli remain suppressed. In this study, using CFS, we examined whether the contrast thresholds for detecting visual looming stimuli are influenced by a congruent auditory stimulus. In Experiment 1, we show that a looming visual stimulus can result in lower detection thresholds compared to a static concentric grating, but that auditory tone pips congruent with the looming stimulus did not lower suppression thresholds any further. In Experiments 2, 3, and 4, we again observed no advantage for congruent multisensory stimuli. These results add to our understanding of the conditions under which multisensory integration is possible, and suggest that certain forms of multisensory integration are not evident when the visual stimulus is suppressed from awareness using CFS.
Saberi, Kourosh; Petrosyan, Agavni
The auditory systems of humans and many other species use the difference in the time of arrival of acoustic signals at the two ears to compute the lateral position of sound sources. This computation is assumed to initially occur in an assembly of neurons organized along a frequency-by-delay surface. Mathematically, the computations are equivalent to a two-dimensional cross-correlation of the input signals at the two ears, with the position of the peak activity along this surface designating the position of the source in space. In this study, partially correlated signals to the two ears are used to probe the mechanisms for encoding spatial cues in stationary or dynamic (moving) signals. It is demonstrated that a cross-correlation model of the auditory periphery coupled with statistical decision theory can predict the patterns of performance by human subjects for both stationary and motion stimuli as a function of stimulus decorrelation. Implications of these findings for the existence of a unique cortical motion system are discussed.
Bruck, Dorothy; Ball, Michelle; Thomas, Ian; Rouillard, Vincent
How arousal thresholds vary with different sounds is a critical issue for emergency awakenings, especially as sleepers are dying in fires despite having a working smoke alarm. Previous research shows that the current high-pitched (3000+ Hz) smoke alarm signal is significantly less effective than an alternative signal, the 520 Hz square wave, in all populations tested. However, as the number of sounds tested has been small further research is needed. Here we measured auditory arousal thresholds (AATs) across signals with a range of characteristics to determine the most effective waking signal. Thirty-nine young adults participated over three nights. In Part A, nine signals were presented in stage 4 sleep with ascending decibel levels. Signals were short beeps in the low- to mid-frequency range with different spectral complexities: square waves, pure tones, whoops and white noise. Part B manipulated temporal patterns, inserting silences of 0, 10 and 21 s after each 12 s of beeps. It was found that the low-frequency (400 and 520 Hz) square waves yielded significantly lower AATs than the alternatives. A trend was found across the three temporal manipulations, with a 10 s intervening silence showing some advantage. These findings support earlier research indicating that the best sound for awakening from deep sleep is a low-frequency square wave. It is argued that the signal with the lowest response threshold when awake may be the same as the most arousing signal when asleep, especially where the sleeper processes the signal as meaningful.
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.
Chi, Chia-Fen; Dewi, Ratna Sari; Surbakti, Yopie Yutama; Hsieh, Dong-Yu
The current study applied Structural Equation Modelling to analyse the relationship among pitch, loudness, tempo and timbre and their relationship with perceived sound quality. Twenty-eight auditory signals of horn, indicator, door open warning and parking sensor were collected from 11 car brands. Twenty-one experienced drivers were recruited to evaluate all sound signals with 11 semantic differential scales. The results indicate that for the continuous sounds, pitch, loudness and timbre each had a direct impact on the perceived quality. Besides the direct impacts, pitch also had an impact on loudness perception. For the intermittent sounds, tempo and timbre each had a direct impact on the perceived quality. These results can help to identify the psychoacoustic attributes affecting the consumers' quality perception and help to design preferable sounds for vehicles. In the end, a design guideline is proposed for the development of auditory signals that adopts the current study's research findings as well as those of other relevant research. Practitioner Summary: This study applied Structural Equation Modelling to analyse the relationship among pitch, loudness, tempo and timbre and their relationship with perceived sound quality. The result can help to identify psychoacoustic attributes affecting the consumers' quality perception and help to design preferable sounds for vehicles.
Park, Hyojin; Ince, Robin A A; Schyns, Philippe G; Thut, Gregor; Gross, Joachim
Humans show a remarkable ability to understand continuous speech even under adverse listening conditions. This ability critically relies on dynamically updated predictions of incoming sensory information, but exactly how top-down predictions improve speech processing is still unclear. Brain oscillations are a likely mechanism for these top-down predictions [1, 2]. Quasi-rhythmic components in speech are known to entrain low-frequency oscillations in auditory areas [3, 4], and this entrainment increases with intelligibility . We hypothesize that top-down signals from frontal brain areas causally modulate the phase of brain oscillations in auditory cortex. We use magnetoencephalography (MEG) to monitor brain oscillations in 22 participants during continuous speech perception. We characterize prominent spectral components of speech-brain coupling in auditory cortex and use causal connectivity analysis (transfer entropy) to identify the top-down signals driving this coupling more strongly during intelligible speech than during unintelligible speech. We report three main findings. First, frontal and motor cortices significantly modulate the phase of speech-coupled low-frequency oscillations in auditory cortex, and this effect depends on intelligibility of speech. Second, top-down signals are significantly stronger for left auditory cortex than for right auditory cortex. Third, speech-auditory cortex coupling is enhanced as a function of stronger top-down signals. Together, our results suggest that low-frequency brain oscillations play a role in implementing predictive top-down control during continuous speech perception and that top-down control is largely directed at left auditory cortex. This suggests a close relationship between (left-lateralized) speech production areas and the implementation of top-down control in continuous speech perception. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
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.
von Trapp, Gardiner; Buran, Bradley N; Sen, Kamal; Semple, Malcolm N; Sanes, Dan H
The detection of a sensory stimulus arises from a significant change in neural activity, but a sensory neuron's response is rarely identical to successive presentations of the same stimulus. Large trial-to-trial variability would limit the central nervous system's ability to reliably detect a stimulus, presumably affecting perceptual performance. However, if response variability were to decrease while firing rate remained constant, then neural sensitivity could improve. Here, we asked whether engagement in an auditory detection task can modulate response variability, thereby increasing neural sensitivity. We recorded telemetrically from the core auditory cortex of gerbils, both while they engaged in an amplitude-modulation detection task and while they sat quietly listening to the identical stimuli. Using a signal detection theory framework, we found that neural sensitivity was improved during task performance, and this improvement was closely associated with a decrease in response variability. Moreover, units with the greatest change in response variability had absolute neural thresholds most closely aligned with simultaneously measured perceptual thresholds. Our findings suggest that the limitations imposed by response variability diminish during task performance, thereby improving the sensitivity of neural encoding and potentially leading to better perceptual sensitivity. The detection of a sensory stimulus arises from a significant change in neural activity. However, trial-to-trial variability of the neural response may limit perceptual performance. If the neural response to a stimulus is quite variable, then the response on a given trial could be confused with the pattern of neural activity generated when the stimulus is absent. Therefore, a neural mechanism that served to reduce response variability would allow for better stimulus detection. By recording from the cortex of freely moving animals engaged in an auditory detection task, we found that variability
Full Text Available Previous studies using binocular rivalry have shown that signals in a modality other than the visual can bias dominance durations depending on their congruency with the rivaling stimuli. More recently, studies using continuous flash suppression (CFS have reported that multisensory integration influences how long visual stimuli remain suppressed. In this study, using CFS, we examined whether the contrast thresholds for detecting visual looming stimuli are influenced by a congruent auditory stimulus. In Experiment 1, we show that a looming visual stimulus can result in lower detection thresholds compared to a static concentric grating, but that auditory tone pips congruent with the looming stimulus did not lower suppression thresholds any further. In Experiments 2, 3, and 4, we again observed no advantage for congruent multisensory stimuli. These results add to our understanding of the conditions under which multisensory integration is possible, and suggest that certain forms of multisensory integration are not evident when the visual stimulus is suppressed from awareness using CFS.
Full Text Available BACKGROUND: Animals that communicate by sound face the problem that the signals arriving at the receiver often are degraded and masked by noise. Frequency filters in the receiver's auditory system may improve the signal-to-noise ratio (SNR by excluding parts of the spectrum which are not occupied by the species-specific signals. This solution, however, is hardly amenable to species that produce broad band signals or have ears with broad frequency tuning. In mammals auditory filters exist that work in the temporal domain of amplitude modulations (AM. Do insects also use this type of filtering? PRINCIPAL FINDINGS: Combining behavioural and neurophysiological experiments we investigated whether AM filters may improve the recognition of masked communication signals in grasshoppers. The AM pattern of the sound, its envelope, is crucial for signal recognition in these animals. We degraded the species-specific song by adding random fluctuations to its envelope. Six noise bands were used that differed in their overlap with the spectral content of the song envelope. If AM filters contribute to reduced masking, signal recognition should depend on the degree of overlap between the song envelope spectrum and the noise spectra. Contrary to this prediction, the resistance against signal degradation was the same for five of six masker bands. Most remarkably, the band with the strongest frequency overlap to the natural song envelope (0-100 Hz impaired acceptance of degraded signals the least. To assess the noise filter capacities of single auditory neurons, the changes of spike trains as a function of the masking level were assessed. Increasing levels of signal degradation in different frequency bands led to similar changes in the spike trains in most neurones. CONCLUSIONS: There is no indication that auditory neurones of grasshoppers are specialized to improve the SNR with respect to the pattern of amplitude modulations.
Animal acoustic communication commonly takes place under masked conditions. For instance, sound signals relevant for mating and survival are very often masked by background noise, which makes their detection and recognition by organisms difficult. Ambient noise (AN) varies in level and shape among different habitats, but also remarkable variations in time and space occurs within the same habitat. Variable AN conditions mask hearing thresholds of the receiver in complex and unpredictable ways, thereby causing distortions in sound perception. When communication takes place in a noisy environment, a highly sensitive system might confer no advantage to the receiver compared to a less sensitive one. The effects of noise masking on auditory thresholds and hearing-related functions are well known, and the potential role of AN in the evolution of the species' auditory sensitivity has been recognized by few authors. The mechanism of the underlying selection process has never been explored, however. Here I present a simple fitness model that seeks for the best sensitivity of a hearing system performing the detection and recognition of the sound under variable AN conditions. The model predicts higher sensitivity (i.e. lower hearing thresholds) as best strategy for species living in quiet habitats and lower sensitivity (i.e. higher hearing thresholds) as best strategy for those living in noisy habitats provided the cost of incorrect recognition is not low. The tradeoff between detection and recognition of acoustic signals appears to be a key factor determining the best level of hearing sensitivity of a species when acoustic communication is corrupted by noise. Copyright © 2015 Elsevier Ltd. All rights reserved.
Reijden, C.S. van der; Mens, L.H.M.; Snik, A.F.M.
OBJECTIVE: To identify EEG derivations that yield high signal-to-noise ratios (SNRs) of the auditory steady-state response (ASSR) in infants aged 0 to 5 months. DESIGN: The ASSR was recorded simultaneously from 10 EEG derivations in a monopolar montage in 20 sleeping infants. Stimuli were tones of
Reijden, C.S. van der; Mens, L.H.M.; Snik, A.F.M.
The Auditory Steady-State Response (ASSR) was recorded in 20 awake adults with normal hearing on ten EEG channels simultaneously to find derivations with the best signal-to-noise ratios (SNRs). Stimuli were 20% frequency modulated tones of 0.5 and 2 kHz at 20 dB SL, 100% amplitude modulated at 90 or
Namazi, Hamidreza; Khosrowabadi, Reza; Hussaini, Jamal; Habibi, Shaghayegh; Farid, Ali Akhavan; Vladimir V. Kulish
One of the major challenges in brain research is to relate the structural features of the auditory stimulus to structural features of Electroencephalogram (EEG) signal. Memory content is an important feature of EEG signal and accordingly the brain. On the other hand, the memory content can also be considered in case of stimulus. Beside all works done on analysis of the effect of stimuli on human EEG and brain memory, no work discussed about the stimulus memory and also the relationship that m...
Henry, Kenneth S; Heinz, Michael G
People with sensorineural hearing loss have substantial difficulty understanding speech under degraded listening conditions. Behavioral studies suggest that this difficulty may be caused by changes in auditory processing of the rapidly-varying temporal fine structure (TFS) of acoustic signals. In this paper, we review the presently known effects of sensorineural hearing loss on processing of TFS and slower envelope modulations in the peripheral auditory system of mammals. Cochlear damage has relatively subtle effects on phase locking by auditory-nerve fibers to the temporal structure of narrowband signals under quiet conditions. In background noise, however, sensorineural loss does substantially reduce phase locking to the TFS of pure-tone stimuli. For auditory processing of broadband stimuli, sensorineural hearing loss has been shown to severely alter the neural representation of temporal information along the tonotopic axis of the cochlea. Notably, auditory-nerve fibers innervating the high-frequency part of the cochlea grow increasingly responsive to low-frequency TFS information and less responsive to temporal information near their characteristic frequency (CF). Cochlear damage also increases the correlation of the response to TFS across fibers of varying CF, decreases the traveling-wave delay between TFS responses of fibers with different CFs, and can increase the range of temporal modulation frequencies encoded in the periphery for broadband sounds. Weaker neural coding of temporal structure in background noise and degraded coding of broadband signals along the tonotopic axis of the cochlea are expected to contribute considerably to speech perception problems in people with sensorineural hearing loss. This article is part of a Special Issue entitled "Annual Reviews 2013". Copyright © 2013 Elsevier B.V. All rights reserved.
Schmidt-Kassow, Maren; Wilkinson, David; Denby, Emma; Ferguson, Heather
The perception of beat within an auditory rhythm can be facilitated when accompanied by synchronised movements. Electrophysiological investigation shows that this facilitatory effect is associated with a larger P300 amplitude. It has remained unclear, however, which movement-related processes drive this P300 effect. To investigate whether vestibular signals play a role, we administered alternating, sub-sensory (mean=.3mA) galvanic current to the vestibular nerves of participants while they counted the number of oddballs presented in a stream of tones played at a rate of 1Hz. Consistent with a vestibular effect, the P300 elicited by the oddballs was increased during stimulation relative to a sham condition, but only when the frequency of the alternating current matched that at which the tones were played. This finding supports the general idea that the vestibular system is involved in audio-motor synchronisation and is the first to show by electrophysiological means that it influences cognitive processes involved in beat perception. Copyright © 2016 Elsevier B.V. All rights reserved.
Antti K O Paukkunen
Full Text Available Reliable measurements are mandatory in clinically relevant auditory event-related potential (AERP-based tools and applications. The comparability of the results gets worse as a result of variations in the remaining measurement error. A potential method is studied that allows optimization of the length of the recording session according to the concurrent quality of the recorded data. In this way, the sufficiency of the trials can be better guaranteed, which enables control of the remaining measurement error. The suggested method is based on monitoring the signal-to-noise ratio (SNR and remaining measurement error which are compared to predefined threshold values. The SNR test is well defined, but the criterion for the measurement error test still requires further empirical testing in practice. According to the results, the reproducibility of average AERPs in repeated experiments is improved in comparison to a case where the number of recorded trials is constant. The test-retest reliability is not significantly changed on average but the between-subject variation in the value is reduced by 33-35%. The optimization of the number of trials also prevents excessive recordings which might be of practical interest especially in the clinical context. The efficiency of the method may be further increased by implementing online tools that improve data consistency.
Paukkunen, Antti K. O.; Leminen, Miika M.; Sepponen, Raimo
Reliable measurements are mandatory in clinically relevant auditory event-related potential (AERP)-based tools and applications. The comparability of the results gets worse as a result of variations in the remaining measurement error. A potential method is studied that allows optimization of the length of the recording session according to the concurrent quality of the recorded data. In this way, the sufficiency of the trials can be better guaranteed, which enables control of the remaining measurement error. The suggested method is based on monitoring the signal-to-noise ratio (SNR) and remaining measurement error which are compared to predefined threshold values. The SNR test is well defined, but the criterion for the measurement error test still requires further empirical testing in practice. According to the results, the reproducibility of average AERPs in repeated experiments is improved in comparison to a case where the number of recorded trials is constant. The test-retest reliability is not significantly changed on average but the between-subject variation in the value is reduced by 33–35%. The optimization of the number of trials also prevents excessive recordings which might be of practical interest especially in the clinical context. The efficiency of the method may be further increased by implementing online tools that improve data consistency. PMID:20407635
James W Lewis
Full Text Available Whether viewed or heard, an object in action can be segmented from a background scene based on a number of different sensory cues. In the visual system, salient low-level attributes of an image are processed along parallel hierarchies, and involve intermediate stages, such as the lateral occipital cortices, wherein gross-level object form features are extracted prior to stages that show object specificity (e.g. for faces, buildings, or tools. In the auditory system, though relying on a rather different set of low-level signal attributes, a distinct acoustic event or auditory object can also be readily extracted from a background acoustic scene. However, it remains unclear whether cortical processing strategies used by the auditory system similarly extract gross-level aspects of acoustic object form that may be inherent to many real-world sounds. Examining mechanical and environmental action sounds, representing two distinct categories of non-biological and non-vocalization sounds, we had participants assess the degree to which each sound was perceived as a distinct object versus an acoustic scene. Using two functional magnetic resonance imaging (fMRI task paradigms, we revealed bilateral foci along the superior temporal gyri (STG showing sensitivity to the object-ness ratings of action sounds, independent of the category of sound and independent of task demands. Moreover, for both categories of sounds these regions also showed parametric sensitivity to spectral structure variations—a measure of change in entropy in the acoustic signals over time (acoustic form—while only the environmental sounds showed parametric sensitivity to mean entropy measures. Thus, similar to the visual system, the auditory system appears to include intermediate feature extraction stages that are sensitive to the acoustic form of action sounds, and may serve as a stage that begins to dissociate different categories of real-world auditory objects.
Full Text Available OBJECTIVE: An experienced sonographer can by listening to the Doppler audio signals perceive various timbres that distinguish different types of umbilical artery flow despite an unchanged pulsatility index (PI. Our aim was to develop an objective measure of the Doppler audio signals recorded from fetoplacental circulation in a sheep model. METHODS: Various degrees of pathological flow velocity waveforms in the umbilical artery, similar to those in human complicated pregnancies, were induced by microsphere embolization of the placental bed (embolization model, 7 lamb fetuses, 370 Doppler recordings or by fetal hemodilution (anemia model, 4 lamb fetuses, 184 recordings. A subjective 11-step operator auditory scale (OAS was related to conventional Doppler parameters, PI and time average mean velocity (TAM, and to sound frequency analysis of Doppler signals (sound frequency with the maximum energy content [MAXpeak] and frequency band at maximum level minus 15 dB [MAXpeak-15 dB] over several heart cycles. RESULTS: WE FOUND A NEGATIVE CORRELATION BETWEEN THE OAS AND PI: median Rho -0.73 (range -0.35- -0.94 and -0.68 (range -0.57- -0.78 in the two lamb models, respectively. There was a positive correlation between OAS and TAM in both models: median Rho 0.80 (range 0.58-0.95 and 0.90 (range 0.78-0.95, respectively. A strong correlation was found between TAM and the results of sound spectrum analysis; in the embolization model the median r was 0.91 (range 0.88-0.97 for MAXpeak and 0.91 (range 0.82-0.98 for MAXpeak-15 dB. In the anemia model, the corresponding values were 0.92 (range 0.78-0.96 and 0.96 (range 0.89-0.98, respectively. CONCLUSION: Audio-spectrum analysis reflects the subjective perception of Doppler sound signals in the umbilical artery and has a strong correlation to TAM-velocity. This information might be of importance for clinical management of complicated pregnancies as an addition to conventional Doppler parameters.
... role. Auditory cohesion problems: This is when higher-level listening tasks are difficult. Auditory cohesion skills — drawing inferences from conversations, understanding riddles, or comprehending verbal math problems — require heightened auditory processing and language levels. ...
A driving simulator was used to compare the effectiveness of increasing intensity (looming) auditory warning signals with other types of auditory warnings. Auditory warnings have been shown to speed driver reaction time in rear-end collision situations; however, it is not clear which type of signal is the most effective. Although verbal and symbolic (e.g., a car horn) warnings have faster response times than abstract warnings, they often lead to more response errors. Participants (N=20) experienced four nonlooming auditory warnings (constant intensity, pulsed, ramped, and car horn), three looming auditory warnings ("veridical," "early," and "late"), and a no-warning condition. In 80% of the trials, warnings were activated when a critical response was required, and in 20% of the trials, the warnings were false alarms. For the early (late) looming warnings, the rate of change of intensity signaled a time to collision (TTC) that was shorter (longer) than the actual TTC. Veridical looming and car horn warnings had significantly faster brake reaction times (BRT) compared with the other nonlooming warnings (by 80 to 160 ms). However, the number of braking responses in false alarm conditions was significantly greater for the car horn. BRT increased significantly and systematically as the TTC signaled by the looming warning was changed from early to veridical to late. Looming auditory warnings produce the best combination of response speed and accuracy. The results indicate that looming auditory warnings can be used to effectively warn a driver about an impending collision.
Anttonen, Tommi; Kirjavainen, Anna; Belevich, Ilya
Cdc42 regulates the initial establishment of cytoskeletal and junctional structures, but only little is known about its role at later stages of cellular differentiation. We studied Cdc42's role in vivo in auditory supporting cells, epithelial cells with high structural complexity. Cdc42 inactivat......Cdc42 regulates the initial establishment of cytoskeletal and junctional structures, but only little is known about its role at later stages of cellular differentiation. We studied Cdc42's role in vivo in auditory supporting cells, epithelial cells with high structural complexity. Cdc42...
Lewis, James W.; Talkington, William J.; Tallaksen, Katherine C.; Frum, Chris A.
Whether viewed or heard, an object in action can be segmented as a distinct salient event based on a number of different sensory cues. In the visual system, several low-level attributes of an image are processed along parallel hierarchies, involving intermediate stages wherein gross-level object form and/or motion features are extracted prior to stages that show greater specificity for different object categories (e.g., people, buildings, or tools). In the auditory system, though relying on a rather different set of low-level signal attributes, meaningful real-world acoustic events and “auditory objects” can also be readily distinguished from background scenes. However, the nature of the acoustic signal attributes or gross-level perceptual features that may be explicitly processed along intermediate cortical processing stages remain poorly understood. Examining mechanical and environmental action sounds, representing two distinct non-biological categories of action sources, we had participants assess the degree to which each sound was perceived as object-like versus scene-like. We re-analyzed data from two of our earlier functional magnetic resonance imaging (fMRI) task paradigms (Engel et al., 2009) and found that scene-like action sounds preferentially led to activation along several midline cortical structures, but with strong dependence on listening task demands. In contrast, bilateral foci along the superior temporal gyri (STG) showed parametrically increasing activation to action sounds rated as more “object-like,” independent of sound category or task demands. Moreover, these STG regions also showed parametric sensitivity to spectral structure variations (SSVs) of the action sounds—a quantitative measure of change in entropy of the acoustic signals over time—and the right STG additionally showed parametric sensitivity to measures of mean entropy and harmonic content of the environmental sounds. Analogous to the visual system, intermediate stages
Lewis, James W; Talkington, William J; Tallaksen, Katherine C; Frum, Chris A
Whether viewed or heard, an object in action can be segmented as a distinct salient event based on a number of different sensory cues. In the visual system, several low-level attributes of an image are processed along parallel hierarchies, involving intermediate stages wherein gross-level object form and/or motion features are extracted prior to stages that show greater specificity for different object categories (e.g., people, buildings, or tools). In the auditory system, though relying on a rather different set of low-level signal attributes, meaningful real-world acoustic events and "auditory objects" can also be readily distinguished from background scenes. However, the nature of the acoustic signal attributes or gross-level perceptual features that may be explicitly processed along intermediate cortical processing stages remain poorly understood. Examining mechanical and environmental action sounds, representing two distinct non-biological categories of action sources, we had participants assess the degree to which each sound was perceived as object-like versus scene-like. We re-analyzed data from two of our earlier functional magnetic resonance imaging (fMRI) task paradigms (Engel et al., 2009) and found that scene-like action sounds preferentially led to activation along several midline cortical structures, but with strong dependence on listening task demands. In contrast, bilateral foci along the superior temporal gyri (STG) showed parametrically increasing activation to action sounds rated as more "object-like," independent of sound category or task demands. Moreover, these STG regions also showed parametric sensitivity to spectral structure variations (SSVs) of the action sounds-a quantitative measure of change in entropy of the acoustic signals over time-and the right STG additionally showed parametric sensitivity to measures of mean entropy and harmonic content of the environmental sounds. Analogous to the visual system, intermediate stages of the
Schwent, V. L.; Hillyard, S. A.; Galambos, R.
A randomized sequence of tone bursts was delivered to subjects at short inter-stimulus intervals with the tones originating from one of three spatially and frequency specific channels. The subject's task was to count the tones in one of the three channels at a time, ignoring the other two, and press a button after each tenth tone. In different conditions, tones were given at high and low intensities and with or without a background white noise to mask the tones. The N sub 1 component of the auditory vertex potential was found to be larger in response to attended channel tones in relation to unattended tones. This selective enhancement of N sub 1 was minimal for loud tones presented without noise and increased markedly for the lower tone intensity and in noise added conditions.
Evolutionary diversification of the auditory organ sensilla in Neoconocephalus katydids (Orthoptera: Tettigoniidae) correlates with acoustic signal diversification over phylogenetic relatedness and life history.
Strauß, J; Alt, J A; Ekschmitt, K; Schul, J; Lakes-Harlan, R
Neoconocephalus Tettigoniidae are a model for the evolution of acoustic signals as male calls have diversified in temporal structure during the radiation of the genus. The call divergence and phylogeny in Neoconocephalus are established, but in tettigoniids in general, accompanying evolutionary changes in hearing organs are not studied. We investigated anatomical changes of the tympanal hearing organs during the evolutionary radiation and divergence of intraspecific acoustic signals. We compared the neuroanatomy of auditory sensilla (crista acustica) from nine Neoconocephalus species for the number of auditory sensilla and the crista acustica length. These parameters were correlated with differences in temporal call features, body size, life histories and different phylogenetic positions. By this, adaptive responses to shifting frequencies of male calls and changes in their temporal patterns can be evaluated against phylogenetic constraints and allometry. All species showed well-developed auditory sensilla, on average 32-35 between species. Crista acustica length and sensillum numbers correlated with body size, but not with phylogenetic position or life history. Statistically significant correlations existed also with specific call patterns: a higher number of auditory sensilla occurred in species with continuous calls or slow pulse rates, and a longer crista acustica occurred in species with double pulses or slow pulse rates. The auditory sensilla show significant differences between species despite their recent radiation, and morphological and ecological similarities. This indicates the responses to natural and sexual selection, including divergence of temporal and spectral signal properties. Phylogenetic constraints are unlikely to limit these changes of the auditory systems. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.
In speech signals two activities - voiced & unvoiced - are prominently observed, in both the cases of “production speech” from mouth, and “hearing speech” passed through ears-brainstem-and brain. These speech signals are broadly categorized into these two regions: Voiced- nearly periodic in nature; Unvoiced – random noise like in nature. For many speech applications it is most important to distinguish between Voiced and Unvoiced speech. We have collected Speech Auditory Brainstem Responses (A...
Segers, P.C.J.; Verhoeven, L.T.W.
In the present study, it was investigated whether kindergartners with specific language impairment (SLI) and normallanguage achieving (NLA) kindergartners can benefit from slowing down the entire speech signal or part of the speech signal in a synthetic speech discrimination task. Subjects were 19
Tan, Ying; Yu, Dinghui; Busto, Germain U.; Wilson, Curtis; Davis, Ronald L.
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 RNA interference approach. Interfering with β-catenin expression in the adult mushroom body neurons specifically impaired long-term memory without altering short-term memory. The impairment was reversible, rescued with expression of a wi...
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....
Lundbeck, Micha; Hartog, Laura; Grimm, Giso
The influence of hearing aid (HA) signal processing on the perception of spatially dynamic sounds has not been systematically investigated so far. Previously, we observed that for elderly hearing-impaired (EHI) listeners concurrent distractor sounds impaired the detectability of left-right source...
Lundbeck, Micha; Hartog, Laura; Grimm, Giso
The influence of hearing aid (HA) signal processing on the perception of spatially dynamic sounds has not been systematically investigated so far. Previously, we observed that interfering sounds impaired the detectability of left-right source movements and reverberation that of near-far source mo...
Ota, Kristie T.; Monsey, Melissa S.; Wu, Melissa S.; Young, Grace J.; Schafe, Glenn E.
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…
Crommett, L.E.; Pérez Bellido, A.; Yau, J.M.
Our ability to process temporal frequency information by touch underlies our capacity to perceive and discriminate surface textures. Auditory signals, which also provide extensive temporal frequency information, can systematically alter the perception of vibrations on the hand. How auditory signals
Full Text Available We use a relatively simple model of an underground current source co-located with the earthquake hypocenter to estimate the magnitude of the seismotelluric current required to produce observable ground signatures. The Alum Rock earthquake of 31 October 2007, is used as an archetype of a typical California earthquake, and the effects of varying the ground conductivity and length of the current element are examined. Results show that for an observed 30 nT pulse at 1 Hz, the expected seismotelluric current magnitudes fall in the range ~10–100 kA. By setting the detectability threshold to 1 pT, we show that even when large values of ground conductivity are assumed, magnetic signals are readily detectable within a range of 30 km from the epicenter. When typical values of ground conductivity are assumed, the minimum current required to produce an observable signal within a 30 km range was found to be ~1 kA, which is a surprisingly low value. Furthermore, we show that deep nulls in the signal power develop in the non-cardinal directions relative to the orientation of the source current, indicating that a magnetometer station located in those regions may not observe a signal even though it is well within the detectable range. This result underscores the importance of using a network of magnetometers when searching for preseismic electromagnetic signals.
Alexander W Shingleton
Full Text Available Recent studies have indicated that the insulin-signaling pathway controls body and organ size in Drosophila, and most metazoans, by signaling nutritional conditions to the growing organs. The temporal requirements for insulin signaling during development are, however, unknown. Using a temperature-sensitive insulin receptor (Inr mutation in Drosophila, we show that the developmental requirements for Inr activity are organ specific and vary in time. Early in development, before larvae reach the "critical size" (the size at which they commit to metamorphosis and can complete development without further feeding, Inr activity influences total development time but not final body and organ size. After critical size, Inr activity no longer affects total development time but does influence final body and organ size. Final body size is affected by Inr activity from critical size until pupariation, whereas final organ size is sensitive to Inr activity from critical size until early pupal development. In addition, different organs show different sensitivities to changes in Inr activity for different periods of development, implicating the insulin pathway in the control of organ allometry. The reduction in Inr activity is accompanied by a two-fold increase in free-sugar levels, similar to the effect of reduced insulin signaling in mammals. Finally, we find that varying the magnitude of Inr activity has different effects on cell size and cell number in the fly wing, providing a potential linkage between the mode of action of insulin signaling and the distinct downstream controls of cell size and number. We present a model that incorporates the effects of the insulin-signaling pathway into the Drosophila life cycle. We hypothesize that the insulin-signaling pathway controls such diverse effects as total developmental time, total body size and organ size through its effects on the rate of cell growth, and proliferation in different organs.
Manoonpong, Poramate; Pasemann, Frank; Fischer, Joern
. 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...
de Guibert, Clément; Maumet, Camille; Ferré, Jean-Christophe; Jannin, Pierre; Biraben, Arnaud; Allaire, Catherine; Barillot, Christian; Le Rumeur, Elisabeth
In the context of presurgical mapping or investigation of neurological and developmental disorders in children, language fMRI raises the issue of the design of a tasks panel achievable by young disordered children. Most language tasks shown to be efficient with healthy children require metalinguistic or reading abilities, therefore adding attentional, cognitive and academic constraints that may be problematic in this context. This study experimented a panel of four language tasks that did not require high attentional skills, reading, or metalinguistic abilities. Two reference tasks involving auditory stimulation (words generation from category, "category"; auditory responsive naming, "definition") were compared with two new tasks involving visual stimulation. These later were designed to tap spontaneous phonological production, in which the names of pictures to be named involve a phonological difference (e.g. in French poule/boule/moule; "phon-diff") or change of segmentation (e.g. in French car/car-te/car-t-on; "phon-seg"). Eighteen healthy children participated (mean age: 12.7+/-3 years). Data processing involved normalizing the data via a matched pairs pediatric template, and inter-task and region of interest analyses with laterality assessment. The reference tasks predominantly activated the left frontal and temporal core language regions, respectively. The new tasks activated these two regions simultaneously, more strongly for the phon-seg task. The union and intersection of all tasks provided more sensitive or specific maps. The study demonstrates that both reference and new tasks highlight core language regions in children, and that the latter are useful for the mapping of spontaneous phonological processing. The use of several different tasks may improve the sensitivity and specificity of fMRI. Copyright 2010 Elsevier Inc. All rights reserved.
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.
Pillion, Joseph P; Shiffler, Dorothy E; Hoon, Alexander H; Lin, Doris D M
To describe auditory function in an individual with bilateral damage to the temporal and parietal cortex. Case report. A previously healthy 17-year old male is described who sustained extensive cortical injury following an episode of viral meningoencephalitis. He developed status epilepticus and required intubation and multiple anticonvulsants. Serial brain MRIs showed bilateral temporoparietal signal changes reflecting extensive damage to language areas and the first transverse gyrus of Heschl on both sides. The patient was referred for assessment of auditory processing but was so severely impaired in speech processing that he was unable to complete any formal tests of his speech processing abilities. Audiological assessment utilizing objective measures of auditory function established the presence of normal peripheral auditory function and illustrates the importance of the use of objective measures of auditory function in patients with injuries to the auditory cortex. Use of objective measures of auditory function is essential in establishing the presence of normal peripheral auditory function in individuals with cortical damage who may not be able to cooperate sufficiently for assessment utilizing behavioral measures of auditory function.
Toocheck, Corey; Clister, Terri; Shupe, John; Crum, Chelsea; Ravindranathan, Preethi; Lee, Tae-Kyung; Ahn, Jung-Mo; Raj, Ganesh V; Sukhwani, Meena; Orwig, Kyle E; Walker, William H
Testosterone acts though the androgen receptor in Sertoli cells to support germ cell development (spermatogenesis) and male fertility, but the molecular and cellular mechanisms by which testosterone acts are not well understood. Previously, we found that in addition to acting through androgen receptor to directly regulate gene expression (classical testosterone signaling pathway), testosterone acts through a nonclassical pathway via the androgen receptor to rapidly activate kinases that are known to regulate spermatogenesis. In this study, we provide the first evidence that nonclassical testosterone signaling occurs in vivo as the MAP kinase cascade is rapidly activated in Sertoli cells within the testis by increasing testosterone levels in the rat. We find that either classical or nonclassical signaling regulates testosterone-mediated Rhox5 gene expression in Sertoli cells within testis explants. The selective activation of classical or nonclassical signaling pathways in Sertoli cells within testis explants also resulted in the differential activation of the Zbtb16 and c-Kit genes in adjacent spermatogonia germ cells. Delivery of an inhibitor of either pathway to Sertoli cells of mouse testes disrupted the blood-testis barrier that is essential for spermatogenesis. Furthermore, an inhibitor of nonclassical testosterone signaling blocked meiosis in pubertal mice and caused the loss of meiotic and postmeiotic germ cells in adult mouse testes. An inhibitor of the classical pathway caused the premature release of immature germ cells. Collectively, these observations indicate that classical and nonclassical testosterone signaling regulate overlapping and distinct functions that are required for the maintenance of spermatogenesis and male fertility. © 2016 by the Society for the Study of Reproduction, Inc.
Brauchli, Christian; Elmer, Stefan; Rogenmoser, Lars; Burkhard, Anja; Jäncke, Lutz
Auditory-visual (AV) synesthesia is a rare phenomenon in which an auditory stimulus induces a "concurrent" color sensation. Current neurophysiological models of synesthesia mainly hypothesize "hyperconnected" and "hyperactivated" brains, but differ in the directionality of signal transmission. The two-stage model proposes bottom-up signal transmission from inducer- to concurrent- to higher-order brain areas, whereas the disinhibited feedback model postulates top-down signal transmission from inducer- to higher-order- to concurrent brain areas. To test the different models of synesthesia, we estimated local current density, directed and undirected connectivity patterns in the intracranial space during 2 min of resting-state (RS) EEG in 11 AV synesthetes and 11 nonsynesthetes. AV synesthetes demonstrated increased parietal theta, alpha, and lower beta current density compared to nonsynesthetes. Furthermore, AV synesthetes were characterized by increased top-down signal transmission from the superior parietal lobe to the left color processing area V4 in the upper beta frequency band. Analyses of undirected connectivity revealed a global, synesthesia-specific hyperconnectivity in the alpha frequency band. The involvement of the superior parietal lobe even during rest is a strong indicator for its key role in AV synesthesia. By demonstrating top-down signal transmission in AV synesthetes, we provide direct support for the disinhibited feedback model of synesthesia. Finally, we suggest that synesthesia is a consequence of global hyperconnectivity. Hum Brain Mapp 39:522-531, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
Gibbens, Ying Y; Warren, James T; Gilbert, Lawrence I; O'Connor, Michael B
In insects, initiation of metamorphosis requires a surge in the production of the steroid hormone 20-hydroxyecdysone from the prothoracic gland, the primary endocrine organ of juvenile larvae. Here, we show that blocking TGFβ/Activin signaling, specifically in the Drosophila prothoracic gland, results in developmental arrest prior to metamorphosis. The terminal, giant third instar larval phenotype results from a failure to induce the large rise in ecdysteroid titer that triggers metamorphosis. We further demonstrate that activin signaling regulates competence of the prothoracic gland to receive PTTH and insulin signals, and that these two pathways act at the mRNA and post-transcriptional levels, respectively, to control ecdysone biosynthetic enzyme expression. This dual regulatory circuitry may provide a cross-check mechanism to ensure that both developmental and nutritional inputs are synchronized before initiating the final genetic program leading to reproductive adult development. As steroid hormone production in C. elegans and mammals is also influenced by TGFβ/Activin signaling, this family of secreted factors may play a general role in regulating developmental transitions across phyla.
Gibbens, Ying Y.; Warren, James T.; Gilbert, Lawrence I.; O'Connor, Michael B.
In insects, initiation of metamorphosis requires a surge in the production of the steroid hormone 20-hydroxyecdysone from the prothoracic gland, the primary endocrine organ of juvenile larvae. Here, we show that blocking TGFβ/Activin signaling, specifically in the Drosophila prothoracic gland, results in developmental arrest prior to metamorphosis. The terminal, giant third instar larval phenotype results from a failure to induce the large rise in ecdysteroid titer that triggers metamorphosis. We further demonstrate that activin signaling regulates competence of the prothoracic gland to receive PTTH and insulin signals, and that these two pathways act at the mRNA and post-transcriptional levels, respectively, to control ecdysone biosynthetic enzyme expression. This dual regulatory circuitry may provide a cross-check mechanism to ensure that both developmental and nutritional inputs are synchronized before initiating the final genetic program leading to reproductive adult development. As steroid hormone production in C. elegans and mammals is also influenced by TGFβ/Activin signaling, this family of secreted factors may play a general role in regulating developmental transitions across phyla. PMID:21613324
Full Text Available BACKGROUND: Male songbirds learn their songs from an adult tutor when they are young. A network of brain nuclei known as the 'song system' is the likely neural substrate for sensorimotor learning and production of song, but the neural networks involved in processing the auditory feedback signals necessary for song learning and maintenance remain unknown. Determining which regions show preferential responsiveness to the bird's own song (BOS is of great importance because neurons sensitive to self-generated vocalisations could mediate this auditory feedback process. Neurons in the song nuclei and in a secondary auditory area, the caudal medial mesopallium (CMM, show selective responses to the BOS. The aim of the present study is to investigate the emergence of BOS selectivity within the network of primary auditory sub-regions in the avian pallium. METHODS AND FINDINGS: Using blood oxygen level-dependent (BOLD fMRI, we investigated neural responsiveness to natural and manipulated self-generated vocalisations and compared the selectivity for BOS and conspecific song in different sub-regions of the thalamo-recipient area Field L. Zebra finch males were exposed to conspecific song, BOS and to synthetic variations on BOS that differed in spectro-temporal and/or modulation phase structure. We found significant differences in the strength of BOLD responses between regions L2a, L2b and CMM, but no inter-stimuli differences within regions. In particular, we have shown that the overall signal strength to song and synthetic variations thereof was different within two sub-regions of Field L2: zone L2a was significantly more activated compared to the adjacent sub-region L2b. CONCLUSIONS: Based on our results we suggest that unlike nuclei in the song system, sub-regions in the primary auditory pallium do not show selectivity for the BOS, but appear to show different levels of activity with exposure to any sound according to their place in the auditory
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Full Text Available Posttraumatic stress disorder (PTSD is characterized by acute and chronic changes in the stress response, manifested as conditioned fear memory. Previously formed memories that are susceptible to disruption immediately after retrieval undergo a protein synthesis-dependent process to become persistent, termed reconsolidation, a process that is regulated by many distinct molecular mechanisms that control gene expression. Increasing evidence supports the participation of the transcription factor NF-κB in the different phases of memory. Here, we demonstrate that inhibition of NF-κB in the basolateral amygdala (BLA, but not central nucleus of the amygdala, after memory reactivation impairs the retention of amygdala-dependent auditory fear conditioning (AFC. We used two independent pharmacological strategies to disrupt the reconsolidation of AFC. Bilateral intra-BLA infusion of sulfasalazine, an inhibitor of IκB kinase that activates NF-κB, and bilateral intra-BLA infusion of SN50, a direct inhibitor of the NF-κB DNA-binding complex, immediately after retrieval disrupted the reconsolidation of AFC. We also found that systemic pretreatment with sodium butyrate, a histone deacetylase inhibitor that enhances histone acetylation, in the amygdala rescued the disruption of reconsolidation induced by NF-κB inhibition in the BLA. These findings indicate that NF-κB activity in the BLA is required for memory reconsolidation in AFC, suggesting that NF-κB might be a potential pharmacotherapy target for posttraumatic stress disorder.
Rado, R; Terkel, J; Wollberg, Z
Based on morphological and behavioral findings we suggest that the seismic vibratory signals that blind mole-rats (Spalax ehrenbergi) use for intraspecific communication are picked up from the substrate by bone conduction and processed by the auditory system. An alternative hypothesis, raised by others, suggest that these signals are processed by the somatosensory system. We show here that brain stem and middle latency responses evoked by vibrations are similar to those evoked by high-intensity airborne clicks but are larger in their amplitudes, especially when the lower jaw is in close contact with the vibrating substrate. Bilateral deafening of the mole-rat or high-intensity masking noise almost completely eliminated these responses. Deafening also gradually reduced head-drumming behavior until its complete elimination about 4-6 weeks after surgery. Successive vibrations, at a rate of 0.5 vibrations/s, elicited prominent responses. At rates higher than 2 vibrations/s the amplitude of the brain stem response did not change, yet the middle latency response disappeared almost completely. It is concluded that the seismic signals that mole rate use for long distance communication are indeed processed primarily by the auditory system.
Palencia-Desai, Sharina; Rost, Megan S; Schumacher, Jennifer A; Ton, Quynh V; Craig, Michael P; Baltrunaite, Kristina; Koenig, Andrew L; Wang, Jinhu; Poss, Kenneth D; Chi, Neil C; Stainier, Didier Y R; Sumanas, Saulius
Endocardial and myocardial progenitors originate in distinct regions of the anterior lateral plate mesoderm and migrate to the midline where they coalesce to form the cardiac tube. Endocardial progenitors acquire a molecular identity distinct from other vascular endothelial cells and initiate expression of specific genes such as nfatc1. Yet the molecular pathways and tissue interactions involved in establishing endocardial identity are poorly understood. The endocardium develops in tight association with cardiomyocytes. To test for a potential role of the myocardium in endocardial morphogenesis, we used two different zebrafish models deficient in cardiomyocytes: the hand2 mutant and a myocardial-specific genetic ablation method. We show that in hand2 mutants endocardial progenitors migrate to the midline but fail to assemble into a cardiac cone and do not express markers of differentiated endocardium. Endocardial differentiation defects were rescued by myocardial but not endocardial-specific expression of hand2. In metronidazole-treated myl7:nitroreductase embryos, myocardial cells were targeted for apoptosis, which resulted in the loss of endocardial nfatc1 expression. However, endocardial cells were present and retained expression of general vascular endothelial markers. We further identified bone morphogenetic protein (BMP) as a candidate myocardium-derived signal required for endocardial differentiation. Chemical and genetic inhibition of BMP signaling at the tailbud stage resulted in severe inhibition of endocardial differentiation while there was little effect on myocardial development. Heat-shock-induced bmp2b expression rescued endocardial nfatc1 expression in hand2 mutants and in myocardium-depleted embryos. Our results indicate that the myocardium is crucial for endocardial morphogenesis and differentiation, and identify BMP as a signal involved in endocardial differentiation. © 2015. Published by The Company of Biologists Ltd.
...) The indication of signal governing movements from siding to main track with the current of traffic on... single track, or signal governing movements from a siding to a main track signaled for movements in... movements from a siding to a main track signaled for movements in either direction through a spring switch...
Benito-Gonzalez, Ana; Doetzlhofer, Angelika
Mechano-sensory hair cells (HCs), housed in the inner ear cochlea, are critical for the perception of sound. In the mammalian cochlea, differentiation of HCs occurs in a striking basal-to-apical and medial-to-lateral gradient, which is thought to ensure correct patterning and proper function of the auditory sensory epithelium. Recent studies have revealed that Hedgehog signaling opposes HC differentiation and is critical for the establishment of the graded pattern of auditory HC differentiation. However, how Hedgehog signaling interferes with HC differentiation is unknown. Here, we provide evidence that in the murine cochlea, Hey1 and Hey2 control the spatiotemporal pattern of HC differentiation downstream of Hedgehog signaling. It has been recently shown that HEY1 and HEY2, two highly redundant HES-related transcriptional repressors, are highly expressed in supporting cell (SC) and HC progenitors (prosensory cells), but their prosensory function remained untested. Using a conditional double knock-out strategy, we demonstrate that prosensory cells form and proliferate properly in the absence of Hey1 and Hey2 but differentiate prematurely because of precocious upregulation of the pro-HC factor Atoh1. Moreover, we demonstrate that prosensory-specific expression of Hey1 and Hey2 and its subsequent graded downregulation is controlled by Hedgehog signaling in a largely FGFR-dependent manner. In summary, our study reveals a critical role for Hey1 and Hey2 in prosensory cell maintenance and identifies Hedgehog signaling as a novel upstream regulator of their prosensory function in the mammalian cochlea. The regulatory mechanism described here might be a broadly applied mechanism for controlling progenitor behavior in the central and peripheral nervous system. Copyright © 2014 the authors 0270-6474/14/3412865-12$15.00/0.
Suresh, Chandan H; Krishnan, Ananthanarayan; Gandour, Jackson T
Long-term experience enhances neural representation of temporal attributes of pitch in the brainstem and auditory cortex in favorable listening conditions. Herein we examine whether cortical pitch mechanisms shaped by language experience are more resilient to degradation in background noise, and exhibit greater binaural release from masking (BRM). Cortical pitch responses (CPR) were recorded from Mandarin- and English-speaking natives using a Mandarin word exhibiting a high rising pitch (/yi2/). Stimuli were presented diotically in Quiet, and in noise at +5, and 0 dB SNR. CPRs were also recorded in binaural conditions, SONO (where signal and noise were in phase at both ears); or S0Nπ (where signal was in phase and noise 180° out of phase at each ear), using 0 dB SNR. At Fz, both groups showed increase in CPR peak latency and decrease in amplitude with increasing noise level. A language-dependent enhancement of Na-Pb amplitude (Chinese > English) was restricted to Quiet and +5 dB SNR conditions. At T7/T8 electrode sites, Chinese natives exhibited a rightward asymmetry for both CPR components. A language-dependent effect (Chinese > English) was restricted to T8. Regarding BRM, both CPR components showed greater response amplitude for the S0Nπ condition compared to S0N0 across groups. Rightward asymmetry for BRM in the Chinese group indicates experience-dependent recruitment of right auditory cortex. Restriction of the advantage in pitch representation to the quiet and +5 SNR conditions, and the absence of group differences in the binaural release from masking, suggest that language experience affords limited advantage in the neural representation of pitch-relevant information in the auditory cortex under adverse listening conditions. Copyright © 2017 Elsevier B.V. All rights reserved.
Anomal, Renata; de Villers-Sidani, Etienne; Merzenich, Michael M; Panizzutti, Rogerio
Sensory experience powerfully shapes cortical sensory representations during an early developmental "critical period" of plasticity. In the rat primary auditory cortex (A1), the experience-dependent plasticity is exemplified by significant, long-lasting distortions in frequency representation after mere exposure to repetitive frequencies during the second week of life. In the visual system, the normal unfolding of critical period plasticity is strongly dependent on the elaboration of brain-derived neurotrophic factor (BDNF), which promotes the establishment of inhibition. Here, we tested the hypothesis that BDNF signaling plays a role in the experience-dependent plasticity induced by pure tone exposure during the critical period in the primary auditory cortex. Elvax resin implants filled with either a blocking antibody against BDNF or the BDNF protein were placed on the A1 of rat pups throughout the critical period window. These pups were then exposed to 7 kHz pure tone for 7 consecutive days and their frequency representations were mapped. BDNF blockade completely prevented the shaping of cortical tuning by experience and resulted in poor overall frequency tuning in A1. By contrast, BDNF infusion on the developing A1 amplified the effect of 7 kHz tone exposure compared to control. These results indicate that BDNF signaling participates in the experience-dependent plasticity induced by pure tone exposure during the critical period in A1.
Full Text Available Sensory experience powerfully shapes cortical sensory representations during an early developmental "critical period" of plasticity. In the rat primary auditory cortex (A1, the experience-dependent plasticity is exemplified by significant, long-lasting distortions in frequency representation after mere exposure to repetitive frequencies during the second week of life. In the visual system, the normal unfolding of critical period plasticity is strongly dependent on the elaboration of brain-derived neurotrophic factor (BDNF, which promotes the establishment of inhibition. Here, we tested the hypothesis that BDNF signaling plays a role in the experience-dependent plasticity induced by pure tone exposure during the critical period in the primary auditory cortex. Elvax resin implants filled with either a blocking antibody against BDNF or the BDNF protein were placed on the A1 of rat pups throughout the critical period window. These pups were then exposed to 7 kHz pure tone for 7 consecutive days and their frequency representations were mapped. BDNF blockade completely prevented the shaping of cortical tuning by experience and resulted in poor overall frequency tuning in A1. By contrast, BDNF infusion on the developing A1 amplified the effect of 7 kHz tone exposure compared to control. These results indicate that BDNF signaling participates in the experience-dependent plasticity induced by pure tone exposure during the critical period in A1.
Slevc, L Robert; Shell, Alison R
Auditory agnosia refers to impairments in sound perception and identification despite intact hearing, cognitive functioning, and language abilities (reading, writing, and speaking). Auditory agnosia can be general, affecting all types of sound perception, or can be (relatively) specific to a particular domain. Verbal auditory agnosia (also known as (pure) word deafness) refers to deficits specific to speech processing, environmental sound agnosia refers to difficulties confined to non-speech environmental sounds, and amusia refers to deficits confined to music. These deficits can be apperceptive, affecting basic perceptual processes, or associative, affecting the relation of a perceived auditory object to its meaning. This chapter discusses what is known about the behavioral symptoms and lesion correlates of these different types of auditory agnosia (focusing especially on verbal auditory agnosia), evidence for the role of a rapid temporal processing deficit in some aspects of auditory agnosia, and the few attempts to treat the perceptual deficits associated with auditory agnosia. A clear picture of auditory agnosia has been slow to emerge, hampered by the considerable heterogeneity in behavioral deficits, associated brain damage, and variable assessments across cases. Despite this lack of clarity, these striking deficits in complex sound processing continue to inform our understanding of auditory perception and cognition. © 2015 Elsevier B.V. All rights reserved.
Doll, T. J.; Folds, D. J.; Leiker, L. A.
The complete ensembles of auditory signals in selected USAF aircraft (the F-4D, F-15, two models of the F-16, the C-5, and the C-141) are described and evaluated. Human factors research related to the design of speech and non-speech and non-speech auditory signals is reviewed and the fundamentals of speech synthesis technology are described. Major findings are: that auditory signals are not well standardized among the aircraft, even between those with similar combat roles that a relatively large number of non-speech auditory signals are used, which may make it difficult for the aircrew to recall the meanings of all the signals; that some non-speech signals are sufficiently similar that they may be confused, particularly in high workload and stressful conditions; and that the criticality of the warnings is not reliably indicated by any characteristic of the signals. Five problem areas requiring further research are discussed: reduction of signal loudness, annoyance, and disruption of other functions; enhancement of the distinctiveness and masking resistance of non-speech signals; effects of concurrent warning signals on aircrew performance in critical operational contexts; additional uses of auditory information in order to relieve visual workload; the need for guidelines for deciding which information should be provided aurally, which should be speech versus non-speech, and for designing speech messages; and optimization of synthesized speech for cockpit applications, including its attention-getting capability, distinctiveness, intelligibility, and ease of comprehension.
Jennings, M B; Shaw, L; Hodgins, H; Kuchar, D A; Bataghva, L Poost-Foroosh
For older workers with acquired hearing loss, this loss as well as the changing nature of work and the workforce, may lead to difficulties and disadvantages in obtaining and maintaining employment. Currently there are very few instruments that can assist workplaces, employers and workers to prepare for older workers with hearing loss or with the evaluation of auditory perception demands of work, especially those relevant to communication, and safety sensitive workplaces that require high levels of communication. This paper introduces key theoretical considerations that informed the development of a new framework, The Audiologic Ergonomic (AE) Framework to guide audiologists, work rehabilitation professionals and workers in developing tools to support the identification and evaluation of auditory perception demands in the workplace, the challenges to communication and the subsequent productivity and safety in the performance of work duties by older workers with hearing loss. The theoretical concepts underpinning this framework are discussed along with next steps in developing tools such as the Canadian Hearing Demands Tool (C-HearD Tool) in advancing approaches to evaluate auditory perception and communication demands in the workplace.
... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RULES, STANDARDS, AND INSTRUCTIONS GOVERNING THE INSTALLATION... installed that each signal governing train movements into a block will display its most restrictive aspect... restrictive state; or when signal control circuit is deenergized. [33 FR 19684, Dec. 25, 1968, as amended at...
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
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.
Kawasaki, Masahiro; Kitajo, Keiichi; Yamaguchi, Yoko
In humans, theta phase (4-8 Hz) synchronization observed on electroencephalography (EEG) plays an important role in the manipulation of mental representations during working memory (WM) tasks; fronto-temporal synchronization is involved in auditory-verbal WM tasks and fronto-parietal synchronization is involved in visual WM tasks. However, whether or not theta phase synchronization is able to select the to-be-manipulated modalities is uncertain. To address the issue, we recorded EEG data from subjects who were performing auditory-verbal and visual WM tasks; we compared the theta synchronizations when subjects performed either auditory-verbal or visual manipulations in separate WM tasks, or performed both two manipulations in the same WM task. The auditory-verbal WM task required subjects to calculate numbers presented by an auditory-verbal stimulus, whereas the visual WM task required subjects to move a spatial location in a mental representation in response to a visual stimulus. The dual WM task required subjects to manipulate auditory-verbal, visual, or both auditory-verbal and visual representations while maintaining auditory-verbal and visual representations. Our time-frequency EEG analyses revealed significant fronto-temporal theta phase synchronization during auditory-verbal manipulation in both auditory-verbal and auditory-verbal/visual WM tasks, but not during visual manipulation tasks. Similarly, we observed significant fronto-parietal theta phase synchronization during visual manipulation tasks, but not during auditory-verbal manipulation tasks. Moreover, we observed significant synchronization in both the fronto-temporal and fronto-parietal theta signals during simultaneous auditory-verbal/visual manipulations. These findings suggest that theta synchronization seems to flexibly connect the brain areas that manipulate WM.
Full Text Available In humans, theta phase (4–8 Hz synchronization observed on electroencephalography (EEG plays an important role in the manipulation of mental representations during working memory (WM tasks; fronto-temporal synchronization is involved in auditory-verbal WM tasks and fronto-parietal synchronization is involved in visual WM tasks. However, whether or not theta phase synchronization is able to select the to-be-manipulated modalities is uncertain. To address the issue, we recorded EEG data from subjects who were performing auditory-verbal and visual WM tasks; we compared the theta synchronizations when subjects performed either auditory-verbal or visual manipulations in separate WM tasks, or performed both two manipulations in the same WM task. The auditory-verbal WM task required subjects to calculate numbers presented by an auditory-verbal stimulus, whereas the visual WM task required subjects to move a spatial location in a mental representation in response to a visual stimulus. The dual WM task required subjects to manipulate auditory-verbal, visual, or both auditory-verbal and visual representations while maintaining auditory-verbal and visual representations. Our time-frequency EEG analyses revealed significant fronto-temporal theta phase synchronization during auditory-verbal manipulation in both auditory-verbal and auditory-verbal/visual WM tasks, but not during visual manipulation tasks. Similarly, we observed significant fronto-parietal theta phase synchronization during visual manipulation tasks, but not during auditory-verbal manipulation tasks. Moreover, we observed significant synchronization in both the fronto-temporal and fronto-parietal theta signals during simultaneous auditory-verbal/visual manipulations. These findings suggest that theta synchronization seems to flexibly connect the brain areas that manipulate WM.
Pinaud, R.; Terleph, T. A.; Wynne, R. D.; Tremere, L. A.
Songbirds have emerged as powerful experimental models for the study of auditory processing of complex natural communication signals. Intact hearing is necessary for several behaviors in developing and adult animals including vocal learning, territorial defense, mate selection and individual recognition. These behaviors are thought to require the processing, discrimination and memorization of songs. Although much is known about the brain circuits that participate in sensorimotor (auditory-vocal) integration, especially the ``song-control" system, less is known about the anatomical and functional organization of central auditory pathways. Here we discuss findings associated with a telencephalic auditory area known as the caudomedial nidopallium (NCM). NCM has attracted significant interest as it exhibits functional properties that may support higher order auditory functions such as stimulus discrimination and the formation of auditory memories. NCM neurons are vigorously dr iven by auditory stimuli. Interestingly, these responses are selective to conspecific, relative to heterospecific songs and artificial stimuli. In addition, forms of experience-dependent plasticity occur in NCM and are song-specific. Finally, recent experiments employing high-throughput quantitative proteomics suggest that complex protein regulatory pathways are engaged in NCM as a result of auditory experience. These molecular cascades are likely central to experience-associated plasticity of NCM circuitry and may be part of a network of calcium-driven molecular events that support the formation of auditory memory traces.
Full Text Available TNF receptor-associated factors (TRAFs are multifunctional adaptor proteins involved in temporal and spatial coordination of signals necessary for normal immune function. Here, we report that TRAF3, a TRAF family member with a key role in Toll-like and TNF family receptor signaling and suppressor of lymphomagenesis, is post-translationally modified by the small ubiquitin-related modifier (SUMO. Through yeast two-hybrid and co-immunoprecipitation assays we have identified Ubc9, the SUMO conjugating enzyme, as a novel TRAF3-interacting protein. We show that Ubc9-dependent SUMOylation of TRAF3 modulates optimal association with the CD40 receptor, thereby influencing TRAF3 degradation and non-canonical NF-κB activation upon CD40 triggering. Collectively, our findings describe a novel post-translational modification of a TRAF family member and reveal a link between SUMOylation and TRAF-mediated signal transduction.
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...
Maier, Joost X; Ghazanfar, Asif A
Looming signals (signals that indicate the rapid approach of objects) are behaviorally relevant signals for all animals. Accordingly, studies in primates (including humans) reveal attentional biases for detecting and responding to looming versus receding signals in both the auditory and visual domains. We investigated the neural representation of these dynamic signals in the lateral belt auditory cortex of rhesus monkeys. By recording local field potential and multiunit spiking activity while the subjects were presented with auditory looming and receding signals, we show here that auditory cortical activity was biased in magnitude toward looming versus receding stimuli. This directional preference was not attributable to the absolute intensity of the sounds nor can it be attributed to simple adaptation, because white noise stimuli with identical amplitude envelopes did not elicit the same pattern of responses. This asymmetrical representation of looming versus receding sounds in the lateral belt auditory cortex suggests that it is an important node in the neural network correlate of looming perception.
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.
...) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RULES, STANDARDS, AND INSTRUCTIONS GOVERNING... opposing signals immediately ahead of it to display the most restrictive aspect, the indication of which... signal in advance of each such signal then displays an aspect requiring a stop, or its most restrictive...
... 47 Telecommunication 1 2010-10-01 2010-10-01 false EAS code and Attention Signal Transmission... SYSTEM (EAS) Emergency Operations § 11.51 EAS code and Attention Signal Transmission requirements. (a... without the Attention Signal and emergency message for State and local emergencies. Pauses in video...
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.
Maria Neimark Geffen
Full Text Available Many natural signals, including environmental sounds, exhibit scale-invariant statistics: their structure is repeated at multiple scales. Such scale invariance has been identified separately across spectral and temporal correlations of natural sounds (Clarke and Voss, 1975; Attias and Schreiner, 1997; Escabi et al., 2003; Singh and Theunissen, 2003. Yet the role of scale-invariance across overall spectro-temporal structure of the sound has not been explored directly in auditory perception. Here, we identify that the sound wave of a recording of running water is a self-similar fractal, exhibiting scale-invariance not only within spectral channels, but also across the full spectral bandwidth. The auditory perception of the water sound did not change with its scale. We tested the role of scale-invariance in perception by using an artificial sound, which could be rendered scale-invariant. We generated a random chirp stimulus: an auditory signal controlled by two parameters, Q, controlling the relative, and r, controlling the absolute, temporal structure of the sound. Imposing scale-invariant statistics on the artificial sound was required for its perception as natural and water-like. Further, Q had to be restricted to a specific range for the sound to be perceived as natural. To detect self-similarity in the water sound, and identify Q, the auditory system needs to process the temporal dynamics of the waveform across spectral bands in terms of the number of cycles, rather than absolute timing. We propose a two-stage neural model implementing this computation. This computation may be carried out by circuits of neurons in the auditory cortex. The set of auditory stimuli developed in this study are particularly suitable for measurements of response properties of neurons in the auditory pathway, allowing for quantification of the effects of varying the statistics of the spectro-temporal statistical structure of the stimulus.
Schwent, V. L.; Hillyard, S. A.; Galambos, R.
The effects of varying the rate of delivery of dichotic tone pip stimuli on selective attention measured by evoked-potential amplitudes and signal detectability scores were studied. The subjects attended to one channel (ear) of tones, ignored the other, and pressed a button whenever occasional targets - tones of a slightly higher pitch were detected in the attended ear. Under separate conditions, randomized interstimulus intervals were short, medium, and long. Another study compared the effects of attention on the N1 component of the auditory evoked potential for tone pips presented alone and when white noise was added to make the tones barely above detectability threshold in a three-channel listening task. Major conclusions are that (1) N1 is enlarged to stimuli in an attended channel only in the short interstimulus interval condition (averaging 350 msec), (2) N1 and P3 are related to different modes of selective attention, and (3) attention selectivity in multichannel listening task is greater when tones are faint and/or difficult to detect.
Halvorson, W.L.; Castellanos, A.E.; Murrieta-Saldivar, J.
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.
Xu, Jinghong; Yu, Liping; Cai, Rui; Zhang, Jiping; Sun, Xinde
Previous studies have shown that the functional development of auditory system is substantially influenced by the structure of environmental acoustic inputs in early life. In our present study, we investigated the effects of early auditory enrichment with music on rat auditory discrimination learning. We found that early auditory enrichment with music from postnatal day (PND) 14 enhanced learning ability in auditory signal-detection task and in sound duration-discrimination task. In parallel, a significant increase was noted in NMDA receptor subunit NR2B protein expression in the auditory cortex. Furthermore, we found that auditory enrichment with music starting from PND 28 or 56 did not influence NR2B expression in the auditory cortex. No difference was found in the NR2B expression in the inferior colliculus (IC) between music-exposed and normal rats, regardless of when the auditory enrichment with music was initiated. Our findings suggest that early auditory enrichment with music influences NMDA-mediated neural plasticity, which results in enhanced auditory discrimination learning.
Strait, Dana L; Kraus, Nina
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 non-musicians. Outcomes indicate strengthened brain networks for selective auditory attention in musicians in that musicians but not non-musicians demonstrate decreased prefrontal response variability with auditory attention. Results are interpreted in the context of previous work 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 and maintenance of language-related skills, musical training may aid in the prevention, habilitation, and remediation of individuals with a wide range of attention-based language, listening and learning impairments.
Dana L Strait
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.
Ghuntla Tejas P.; Mehta Hemant B.; Gokhale Pradnya A.; Shah Chinmay J.
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...
Goutte, Sandra; Mason, Matthew J; Christensen-Dalsgaard, Jakob
The emergence and maintenance of animal communication systems requires the co-evolution of signal and receiver. Frogs and toads rely heavily on acoustic communication for coordinating reproduction and typically have ears tuned to the dominant frequency of their vocalizations, allowing discriminat......The emergence and maintenance of animal communication systems requires the co-evolution of signal and receiver. Frogs and toads rely heavily on acoustic communication for coordinating reproduction and typically have ears tuned to the dominant frequency of their vocalizations, allowing...... by their high toxicity might help to explain why calling has not yet disappeared, and that visual communication may have replaced auditory in these colourful, diurnal frogs....
Das, P; Maduzia, L L; Wang, H; Finelli, A L; Cho, S H; Smith, M M; Padgett, R W
Signals from transforming growth factor-beta (TGF-beta) ligands are transmitted within the cell by members of the Smad family, which can be grouped into three classes based on sequence similarities. Our previous identification of both class I and II Smads functioning in a single pathway in C. elegans, raised the issue of whether the requirement for Smads derived from different classes is a general feature of TGF-beta signaling. We report here the identification of a new Drosophila class II Smad, Medea, a close homolog of the human tumor-suppressor gene DPC4. Embryos from germline clones of both Medea and Mad (a class I Smad) are ventralized, as are embryos null for the TGF-beta-like ligand decapentaplegic (dpp). Loss of Medea also blocks dpp signaling during later development, suggesting that Medea, like Mad, is universally required for dpp signaling. Furthermore, we show that the necessity for these two closely related, non-redundant Smads, is due to their different signaling properties - upon activation of the Dpp pathway, Mad is required to actively translocate Medea into the nucleus. These results provide a paradigm for, and distinguish between, the requirement for class I and II Smads in Dpp/BMP signaling.
Ian T. Zajac
Full Text Available This study examined whether the broad ability general speediness (Gs could be measured via the auditory modality. Existing and purpose-developed auditory tasks that maintained the cognitive requirements of established visually presented Gs markers were completed by 96 university undergraduates. Exploratory and confirmatory factor analyses showed that the auditory tasks combined with established visual measures to define latent Gs and reaction time factors. These findings provide preliminary evidence that suggests that if auditory tasks are developed that maintain the same cognitive requirements as existing visual measures, then they are likely to index similar cognitive processes.
Scott, Brian H; Mishkin, Mortimer
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. Published by Elsevier B.V.
Ahnfelt-Rønne, Jonas; Ravassard, Philippe; Pardanaud-Glavieux, Corinne; Scharfmann, Raphaél; Serup, Palle
OBJECTIVE Pancreas organogenesis is orchestrated by interactions between the epithelium and the mesenchyme, but these interactions are not completely understood. Here we investigated a role for bone morphogenetic protein (BMP) signaling within the pancreas mesenchyme and found it to be required for the normal development of the mesenchyme as well as for the pancreatic epithelium. RESEARCH DESIGN AND METHODS We analyzed active BMP signaling by immunostaining for phospho-Smad1,5,8 and tested whether pancreas development was affected by BMP inhibition after expression of Noggin and dominant negative BMP receptors in chicken and mouse pancreas. RESULTS Endogenous BMP signaling is confined to the mesenchyme in the early pancreas and inhibition of BMP signaling results in severe pancreatic hypoplasia with reduced epithelial branching. Notably, we also observed an excessive endocrine differentiation when mesenchymal BMP signaling is blocked, presumably secondary to defective mesenchyme to epithelium signaling. CONCLUSIONS We conclude that BMP signaling plays a previously unsuspected role in the mesenchyme, required for normal development of the mesenchyme as well as for the epithelium. PMID:20522595
Sanjuán Juaristi, Julio; Sanjuán Martínez-Conde, Mar
Given the relevance of possible hearing losses due to sound overloads and the short list of references of objective procedures for their study, we provide a technique that gives precise data about the audiometric profile and recruitment factor. Our objectives were to determine peripheral fatigue, through the cochlear microphonic response to sound pressure overload stimuli, as well as to measure recovery time, establishing parameters for differentiation with regard to current psychoacoustic and clinical studies. We used specific instruments for the study of cochlear microphonic response, plus a function generator that provided us with stimuli of different intensities and harmonic components. In Wistar rats, we first measured the normal microphonic response and then the effect of auditory fatigue on it. Using a 60dB pure tone acoustic stimulation, we obtained a microphonic response at 20dB. We then caused fatigue with 100dB of the same frequency, reaching a loss of approximately 11dB after 15minutes; after that, the deterioration slowed and did not exceed 15dB. By means of complex random tone maskers or white noise, no fatigue was caused to the sensory receptors, not even at levels of 100dB and over an hour of overstimulation. No fatigue was observed in terms of sensory receptors. Deterioration of peripheral perception through intense overstimulation may be due to biochemical changes of desensitisation due to exhaustion. Auditory fatigue in subjective clinical trials presumably affects supracochlear sections. The auditory fatigue tests found are not in line with those obtained subjectively in clinical and psychoacoustic trials. Copyright © 2013 Elsevier España, S.L.U. y Sociedad Española de Otorrinolaringología y Patología Cérvico-Facial. All rights reserved.
Neugebauer, Judith M; Yost, H Joseph
Early disruption of FGF signaling alters left-right (LR) asymmetry throughout the embryo. Here we uncover a role for FGF signaling that specifically disrupts brain asymmetry, independent of normal lateral plate mesoderm (LPM) asymmetry. When FGF signaling is inhibited during mid-somitogenesis, asymmetrically expressed LPM markers southpaw and lefty2 are not affected. However, asymmetrically expressed brain markers lefty1 and cyclops become bilateral. We show that FGF signaling controls expression of six3b and six7, two transcription factors required for repression of asymmetric lefty1 in the brain. We found that Z0-1, atypical PKC (aPKC) and β-catenin protein distribution revealed a midline structure in the forebrain that is dependent on a balance of FGF signaling. Ectopic activation of FGF signaling leads to overexpression of six3b, loss of organized midline adherins junctions and bilateral loss of lefty1 expression. Reducing FGF signaling leads to a reduction in six3b and six7 expression, an increase in cell boundary formation in the brain midline, and bilateral expression of lefty1. Together, these results suggest a novel role for FGF signaling in the brain to control LR asymmetry, six transcription factor expressions, and a midline barrier structure. Copyright © 2013 Elsevier Inc. All rights reserved.
Full Text Available Auditory Hallucination or Paracusia is a form of hallucination that involves perceiving sounds without auditory stimulus. A common is hearing one or more talking voices which is associated with psychotic disorders such as schizophrenia or mania. Hallucination, itself, is the most common feature of perceiving the wrong stimulus or to the better word perception of the absence stimulus. Here we will discuss four definitions of hallucinations:1.Perceiving of a stimulus without the presence of any subject; 2. hallucination proper which are the wrong perceptions that are not the falsification of real perception, Although manifest as a new subject and happen along with and synchronously with a real perception;3. hallucination is an out-of-body perception which has no accordance with a real subjectIn a stricter sense, hallucinations are defined as perceptions in a conscious and awake state in the absence of external stimuli which have qualities of real perception, in that they are vivid, substantial, and located in external objective space. We are going to discuss it in details here.
Demehri, Shadmehr; Kopan, Raphael
Summary Notch signaling plays an important role in hair follicle maintenance, and it has been suggested that Notch is also required for follicular fate selection by adult hair follicle stem cells in the bulge. Here we demonstrate that, on the contrary, Notch signaling in bi-potential bulge stem cells or their uncommitted descendents acts to suppress the epidermal fate choice, thus ensuring follicular fate selection. To examine the role of Notch signaling in adult hair follicle stem cells, we used a Krt1-15-CrePR1 transgenic mouse line to delete Rbpj or all Notch proteins specifically in the bulge stem cells. We conclusively determined that in the absence of Notch signaling, bulge stem cell descendents retain their capacity to execute the follicular differentiation program but fail to maintain it owing to their genetic deficiency. The defect in terminal differentiation caused the diversion of Notch-deficient hair follicles to epidermal cysts, and the presence of wild-type cells could not prevent this conversion. Importantly, our analysis revealed that a functional Notch signaling pathway was required to block bulge stem cells from migrating into, and assuming the fate of, interfollicular epidermis. Taken together, our findings yield detailed insight into the function of Notch signaling in hair follicle stem cells and reveal the mechanism of the replacement of Notch-deficient adult hair follicles by epidermal cysts. PMID:19211676
Fumoto, Katsumi; Takigawa-Imamura, Hisako; Sumiyama, Kenta; Kaneiwa, Tomoyuki; Kikuchi, Akira
In lung development, the apically constricted columnar epithelium forms numerous buds during the pseudoglandular stage. Subsequently, these epithelial cells change shape into the flat or cuboidal pneumocytes that form the air sacs during the canalicular and saccular (canalicular-saccular) stages, yet the impact of cell shape on tissue morphogenesis remains unclear. Here, we show that the expression of Wnt components is decreased in the canalicular-saccular stages, and that genetically constitutive activation of Wnt signaling impairs air sac formation by inducing apical constriction in the epithelium as seen in the pseudoglandular stage. Organ culture models also demonstrate that Wnt signaling induces apical constriction through apical actomyosin cytoskeletal organization. Mathematical modeling reveals that apical constriction induces bud formation and that loss of apical constriction is required for the formation of an air sac-like structure. We identify MAP/microtubule affinity-regulating kinase 1 (Mark1) as a downstream molecule of Wnt signaling and show that it is required for apical cytoskeletal organization and bud formation. These results suggest that Wnt signaling is required for bud formation by inducing apical constriction during the pseudoglandular stage, whereas loss of Wnt signaling is necessary for air sac formation in the canalicular-saccular stages. © 2017. Published by The Company of Biologists Ltd.
Beyer, Tina; Danilchik, Michael; Thumberger, Thomas; Vick, Philipp; Tisler, Matthias; Schneider, Isabelle; Bogusch, Susanne; Andre, Philipp; Ulmer, Bärbel; Walentek, Peter; Niesler, Beate; Blum, Martin; Schweickert, Axel
In vertebrates, most inner organs are asymmetrically arranged with respect to the main body axis . Symmetry breakage in fish, amphibian, and mammalian embryos depends on cilia-driven leftward flow of extracellular fluid during neurulation [2-5]. Flow induces the asymmetric nodal cascade that governs asymmetric organ morphogenesis and placement [1, 6, 7]. In the frog Xenopus, an alternative laterality-generating mechanism involving asymmetric localization of serotonin at the 32-cell stage has been proposed . However, no functional linkage between this early localization and flow at neurula stage has emerged. Here, we report that serotonin signaling is required for specification of the superficial mesoderm (SM), which gives rise to the ciliated gastrocoel roof plate (GRP) where flow occurs [5, 9]. Flow and asymmetry were lost in embryos in which serotonin signaling was downregulated. Serotonin, which we found uniformly distributed along the main body axes in the early embryo, was required for Wnt signaling, which provides the instructive signal to specify the GRP. Importantly, serotonin was required for Wnt-induced double-axis formation as well. Our data confirm flow as primary mechanism of symmetry breakage and suggest a general role of serotonin as competence factor for Wnt signaling during axis formation in Xenopus. Copyright © 2012 Elsevier Ltd. All rights reserved.
Chocarro-Calvo, Ana; Zaballos, Miguel A.; Santisteban, Pilar
Modulation of MAPK signaling duration by cAMP defines its physiological output by driving cells toward proliferation or differentiation. Understanding how the kinetics of MAPK signaling are integrated with other cellular signals is a key issue in development and cancer. Here we show that dopamine and cAMP-regulated neuronal phosphoprotein, 32 kDa (DARPP-32), a protein required for thyroid cell differentiation, determines whether MAPK/ERK activation is sustained or transient. Serum, a stimulus that activates MAPK signaling and does not independently increase DARPP-32 levels results in transient activation of the MAPK pathway. By contrast, TSH + (IGF-I) activate MAPK signaling but also independently increase DARPP-32 levels. Our results are consistent with a model in which maintenance of DARPP-32 expression by TSH + IGF-I leads to sustained MAPK signaling. Moreover, the sensitivity of MAPK/ERK signaling in thyroid cells is lost when de novo DARPP-32 expression is blocked by small interfering RNA. Because both DARPP-32 levels and function as inhibitor of protein phosphatase 1, a key inhibitor of MAPK kinase activity, are governed by cAMP/protein kinase A, the results may explain why in thyroid cells cAMP signaling downstream from TSH controls the duration of MAPK pathway activity. Thus, fine-tuning of DARPP-32 levels leads to changes in the kinetics or sensitivity of MAPK/ERK signaling. Given the implications of MAPK signaling in thyroid cancer and the loss of DARPP-32 in tumor and transformed thyroid cells, DARPP-32 may represent a key therapeutic target. PMID:22301787
Wang, Yidong; Wu, Bingruo; Farrar, Emily; Lui, Wendy; Lu, Pengfei; Zhang, Donghong; Alfieri, Christina M; Mao, Kai; Chu, Ming; Yang, Di; Xu, Di; Rauchman, Michael; Taylor, Verdon; Conway, Simon J; Yutzey, Katherine E; Butcher, Jonathan T; Zhou, Bin
Congenital anomalies of arterial valves are common birth defects, leading to valvar stenosis. With no pharmaceutical treatment that can prevent the disease progression, prosthetic replacement is the only choice of treatment, incurring considerable morbidity and mortality. Animal models presenting localized anomalies and stenosis of congenital arterial valves similar to that of humans are critically needed research tools to uncover developmental molecular mechanisms underlying this devastating human condition. We generated and characterized mouse models with conditionally altered Notch signalling in endothelial or interstitial cells of developing valves. Mice with inactivation of Notch1 signalling in valvar endothelial cells (VEC) developed congenital anomalies of arterial valves including bicuspid aortic valves and valvar stenosis. Notch1 signalling in VEC was required for repressing proliferation and activating apoptosis of valvar interstitial cells (VIC) after endocardial-to-mesenchymal transformation (EMT). We showed that Notch signalling regulated Tnfα expression in vivo, and Tnf signalling was necessary for apoptosis of VIC and post-EMT development of arterial valves. Furthermore, activation or inhibition of Notch signalling in cultured pig aortic VEC-promoted or suppressed apoptosis of VIC, respectively. We have now met the need of critical animal models and shown that Notch-Tnf signalling balances proliferation and apoptosis for post-EMT development of arterial valves. Our results suggest that mutations in its components may lead to congenital anomaly of aortic valves and valvar stenosis in humans.
Münder, Sandra; Tischer, Susanne; Grundhuber, Maresa; Büchels, Nathalie; Bruckmeier, Nadine; Eckert, Stefanie; Seefeldt, Carolin A; Prexl, Andrea; Käsbauer, Tina; Böttger, Angelika
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. © 2013 Elsevier Inc. All rights reserved.
Zhang, Yilu; Weng, Juyang; Hwang, Wey-Shiuan
Motivated by the human autonomous development process from infancy to adulthood, we have built a robot that develops its cognitive and behavioral skills through real-time interactions with the environment. We call such a robot a developmental robot. In this paper, we present the theory and the architecture to implement a developmental robot and discuss the related techniques that address an array of challenging technical issues. As an application, experimental results on a real robot, self-organizing, autonomous, incremental learner (SAIL), are presented with emphasis on its audition perception and audition-related action generation. In particular, the SAIL robot conducts the auditory learning from unsegmented and unlabeled speech streams without any prior knowledge about the auditory signals, such as the designated language or the phoneme models. Neither available before learning starts are the actions that the robot is expected to perform. SAIL learns the auditory commands and the desired actions from physical contacts with the environment including the trainers.
Ruan, Qingwei; Ma, Cheng; Zhang, Ruxin; Yu, Zhuowei
The development of presbycusis, or age-related hearing loss, is determined by a combination of genetic and environmental factors. The auditory periphery exhibits a progressive bilateral, symmetrical reduction of auditory sensitivity to sound from high to low frequencies. The central auditory nervous system shows symptoms of decline in age-related cognitive abilities, including difficulties in speech discrimination and reduced central auditory processing, ultimately resulting in auditory perceptual abnormalities. The pathophysiological mechanisms of presbycusis include excitotoxicity, oxidative stress, inflammation, aging and oxidative stress-induced DNA damage that results in apoptosis in the auditory pathway. However, the originating signals that trigger these mechanisms remain unclear. For instance, it is still unknown whether insulin is involved in auditory aging. Auditory aging has preclinical lesions, which manifest as asymptomatic loss of periphery auditory nerves and changes in the plasticity of the central auditory nervous system. Currently, the diagnosis of preclinical, reversible lesions depends on the detection of auditory impairment by functional imaging, and the identification of physiological and molecular biological markers. However, despite recent improvements in the application of these markers, they remain under-utilized in clinical practice. The application of antisenescent approaches to the prevention of auditory aging has produced inconsistent results. Future research will focus on the identification of markers for the diagnosis of preclinical auditory aging and the development of effective interventions. © 2013 Japan Geriatrics Society.
Wang, Jikui; Rhee, Siyeon; Palaria, Amrita; Tremblay, Kimberly D.
Background The definitive endoderm arises as a naive epithelial sheet that produces the entire gut tube and associated organs including the liver, pancreas and lungs. Murine explant studies demonstrate that Fibroblast Growth Factor (FGF) signaling from adjacent tissues is required to induce hepatic gene expression from isolated foregut endoderm. The requirement of FGF signaling during liver development is examined via small molecule inhibition during whole embryo culture. Results Loss of FGF signaling prior to hepatic induction results in morphological defects and gene expression changes that are confined to the anterior liver bud. In contrast the posterior portion of the liver bud remains relatively unaffected. Because FGF is thought to act as a morphogen during endoderm organogenesis, the ventral pancreas was also examined after FGF inhibition. Although the size of the ventral pancreas is not affected, loss of FGF signaling results in a significantly higher density of ventral pancreas cells. Conclusions The requirement for FGF-mediated induction of hepatic gene expression differs across the anterior-posterior axis of the developing liver bud. These results underscore the importance of studying tissue differentiation in the context of the whole embryo. PMID:25302779
Wang, Jikui; Rhee, Siyeon; Palaria, Amrita; Tremblay, Kimberly D
The definitive endoderm arises as a naive epithelial sheet that produces the entire gut tube and associated organs including the liver, pancreas and lungs. Murine explant studies demonstrate that fibroblast growth factor (FGF) signaling from adjacent tissues is required to induce hepatic gene expression from isolated foregut endoderm. The requirement of FGF signaling during liver development is examined by means of small molecule inhibition during whole embryo culture. Loss of FGF signaling before hepatic induction results in morphological defects and gene expression changes that are confined to the anterior liver bud. In contrast the posterior portion of the liver bud remains relatively unaffected. Because FGF is thought to act as a morphogen during endoderm organogenesis, the ventral pancreas was also examined after FGF inhibition. Although the size of the ventral pancreas is not affected, loss of FGF signaling results in a significantly higher density of ventral pancreas cells. The requirement for FGF-mediated induction of hepatic gene expression differs across the anterior/posterior axis of the developing liver bud. These results underscore the importance of studying tissue differentiation in the context of the whole embryo. © 2014 Wiley Periodicals, Inc.
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
Ferguson, Melanie; Henshaw, Helen
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.
Corwin D. Nelson
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.
Hines, D J; Schmitt, L I; Hines, R M; Moss, S J; Haydon, P G
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 of sleep deprivation. Here, we found that astrocytic signaling to adenosine (A1) receptors was required for the robust reduction of depressive-like behaviors following 12 hours of sleep deprivation. As sleep deprivation activates synaptic A1 receptors, we mimicked the effect of sleep deprivation on depression phenotypes by administration of the A1 agonist CCPA. These results provide the first mechanistic insight into how sleep deprivation impacts mood, and provide a novel pathway for rapid antidepressant development by modulation of glial signaling in the brain.
Nevado, Angel; Hadjipapas, Avgis; Kinsey, Kristofer; Moratti, Stephan; Barnes, Gareth R; Holliday, Ian E; Green, Gary G
An increasing number of neuroimaging studies are concerned with the identification of interactions or statistical dependencies between brain areas. Dependencies between the activities of different brain regions can be quantified with functional connectivity measures such as the cross-correlation coefficient. An important factor limiting the accuracy of such measures is the amount of empirical data available. For event-related protocols, the amount of data also affects the temporal resolution of the analysis. We use analytical expressions to calculate the amount of empirical data needed to establish whether a certain level of dependency is significant when the time series are autocorrelated, as is the case for biological signals. These analytical results are then contrasted with estimates from simulations based on real data recorded with magnetoencephalography during a resting-state paradigm and during the presentation of visual stimuli. Results indicate that, for broadband signals, 50-100 s of data is required to detect a true underlying cross-correlations coefficient of 0.05. This corresponds to a resolution of a few hundred milliseconds for typical event-related recordings. The required time window increases for narrow band signals as frequency decreases. For instance, approximately 3 times as much data is necessary for signals in the alpha band. Important implications can be derived for the design and interpretation of experiments to characterize weak interactions, which are potentially important for brain processing. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
Dietz, Birte; Manahan-Vaughan, Denise
Long-term potentiation (LTP) and long-term depression (LTD) are key cellular processes that support memory formation. Whereas increases of synaptic strength by means of LTP may support the creation of a spatial memory 'engram', LTD appears to play an important role in refining and optimising experience-dependent encoding. A differentiation in the role of hippocampal subfields is apparent. For example, LTD in the dentate gyrus (DG) is enabled by novel learning about large visuospatial features, whereas in area CA1, it is enabled by learning about discrete aspects of spatial content, whereby, both discrete visuospatial and olfactospatial cues trigger LTD in CA1. Here, we explored to what extent local audiospatial cues facilitate information encoding in the form of LTD in these subfields. Coupling of low frequency afferent stimulation (LFS) with discretely localised, novel auditory tones in the sonic hearing, or ultrasonic range, facilitated short-term depression (STD) into LTD (>24 h) in CA1, but not DG. Re-exposure to the now familiar audiospatial configuration ca. 1 week later failed to enhance STD. Reconfiguration of the same audiospatial cues resulted anew in LTD when ultrasound, but not non-ultrasound cues were used. LTD facilitation that was triggered by novel exposure to spatially arranged tones, or to spatial reconfiguration of the same tones were both prevented by an antagonism of the metabotropic glutamate receptor, mGlu5. These data indicate that, if behaviourally salient enough, the hippocampus can use audiospatial cues to facilitate LTD that contributes to the encoding and updating of spatial representations. Effects are subfield-specific, and require mGlu5 activation, as is the case for visuospatial information processing. These data reinforce the likelihood that LTD supports the encoding of spatial features, and that this occurs in a qualitative and subfield-specific manner. They also support that mGlu5 is essential for synaptic encoding of spatial
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
An integral part of global environment change is an increase in the atmospheric concentration of CO2 ([CO2]) . 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  and plant nutrient acquisition , we know comparatively little about the molecular components involved in the intracellular signaling pathways by which [CO2] controls stomatal development and function . 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. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
Carrat, R; Thillier, J L; Durivault, J
The liminal auditory threshold for white noise and for coloured noise was determined from a statistical survey of a group of 21 young people with normal hearing. The normal auditory threshold for white noise with a spectrum covering the whole of the auditory field is between -- 0.57 dB +/- 8.78. The normal auditory threshold for bands of filtered white noise (coloured noise with a central frequency corresponding to the pure frequencies usually employed in tonal audiometry) describes a typical curve which, instead of being homothetic to the usual tonal curves, sinks to low frequencies and then rises. The peak of this curve is replaced by a broad plateau ranging from 750 to 6000 Hz and contained in the concavity of the liminal tonal curves. The ear is therefore less sensitive but, at limited acoustic pressure, white noise first impinges with the same discrimination upon the whole of the conversational zone of the auditory field. Discovery of the audiometric threshold for white noise constitutes a synthetic method of measuring acuteness of hearing which considerably reduces the amount of manipulation required.
Kimberly A. Wong
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.
Pannese, Alessia; Grandjean, Didier; Frühholz, Sascha
Discriminating between auditory signals of different affective value is critical to successful social interaction. It is commonly held that acoustic decoding of such signals occurs in the auditory system, whereas affective decoding occurs in the amygdala. However, given that the amygdala receives direct subcortical projections that bypass the auditory cortex, it is possible that some acoustic decoding occurs in the amygdala as well, when the acoustic features are relevant for affective discrimination. We tested this hypothesis by combining functional neuroimaging with the neurophysiological phenomena of repetition suppression (RS) and repetition enhancement (RE) in human listeners. Our results show that both amygdala and auditory cortex responded differentially to physical voice features, suggesting that the amygdala and auditory cortex decode the affective quality of the voice not only by processing the emotional content from previously processed acoustic features, but also by processing the acoustic features themselves, when these are relevant to the identification of the voice's affective value. Specifically, we found that the auditory cortex is sensitive to spectral high-frequency voice cues when discriminating vocal anger from vocal fear and joy, whereas the amygdala is sensitive to vocal pitch when discriminating between negative vocal emotions (i.e., anger and fear). Vocal pitch is an instantaneously recognized voice feature, which is potentially transferred to the amygdala by direct subcortical projections. These results together provide evidence that, besides the auditory cortex, the amygdala too processes acoustic information, when this is relevant to the discrimination of auditory emotions. Copyright Â© 2016 Elsevier Ltd. All rights reserved.
Jang, Anna C-C; Chang, Yu-Chiuan; Bai, Jianwu; Montell, Denise
During development, elaborate patterns of cell differentiation and movement must occur in the correct locations and at the proper times. Developmental timing has been studied less than spatial pattern formation, and the mechanisms integrating the two are poorly understood. Border-cell migration in the Drosophila ovary occurs specifically at stage 9. Timing of the migration is regulated by the steroid hormone ecdysone, whereas spatial patterning of the migratory population requires localized activity of the JAK-STAT pathway. Ecdysone signalling is patterned spatially as well as temporally, although the mechanisms are not well understood. In stage 9 egg chambers, ecdysone signalling is highest in anterior follicle cells including the border cells. We identify the gene abrupt as a repressor of ecdysone signalling and border-cell migration. Abrupt protein is normally lost from border-cell nuclei during stage 9, in response to JAK-STAT activity. This contributes to the spatial pattern of the ecdysone response. Abrupt attenuates ecdysone signalling by means of a direct interaction with the basic helix-loop-helix (bHLH) domain of the P160 ecdysone receptor coactivator Taiman (Tai). Taken together, these findings provide a molecular mechanism by which spatial and temporal cues are integrated.
An, Lijun; Zhou, Zhongjing; Su, Sha; Yan, An; Gan, Yinbo
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).
Bettini, Matthew L; Chou, Po-Chein; Guy, Clifford S; Lee, Thomas; Vignali, Kate M; Vignali, Dario A A
For the αβ or γδTCR chains to integrate extracellular stimuli into the appropriate intracellular cellular response, they must use the 10 ITAMs found within the CD3 subunits (CD3γε, CD3δε, and ζζ) of the TCR signaling complex. However, it remains unclear whether each specific ITAM sequence of the individual subunit (γεδζ) is required for thymocyte development or whether any particular CD3 ITAM motif is sufficient. In this article, we show that mice utilizing a single ITAM sequence (γ, ε, δ, ζa, ζb, or ζc) at each of the 10 ITAM locations exhibit a substantial reduction in thymic cellularity and limited CD4(-)CD8(-) (double-negative) to CD4(+)CD8(+) (double-positive) maturation because of low TCR expression and signaling. Together, the data suggest that ITAM sequence diversity is required for optimal TCR signal transduction and subsequent T cell maturation. Copyright © 2017 by The American Association of Immunologists, Inc.
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.
Vibhakar C Kotak
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.
Smith, J M; Rowsell, E H; Shioi, J; Taylor, B L
In Escherichia coli and Salmonella typhimurium, ATP is required for chemotaxis and for a normal probability of clockwise rotation of the flagellar motors, in addition to the requirement for S-adenosylmethionine (J. Shioi, R. J. Galloway, M. Niwano, R. E. Chinnock, and B. L. Taylor, J. Biol. Chem. 257:7969-7975, 1982). The site of the ATP requirement was investigated. The times required for S. typhimurium ST23 (hisF) to adapt to a step increase in serine, phenol, or benzoate were similar in cells depleted of ATP and in cells with normal levels of ATP. This established that ATP was not required for the chemotactic signal to cross the inner membrane or for adaptation to the transmembrane signal to occur. Depletion of ATP did not affect the probability of clockwise rotation in E. coli cheYZ scy strains that were defective in the cheY and cheZ genes and had a partially compensating mutation in the motor switch. Strain HCB326 (cheAWRBYZ tar tap tsr trg::Tn10), which was deficient in all chemotaxis components except the switch and motor, was transformed with the pCK63 plasmid (ptac-cheY+). Induction of cheY in the transformant increased the frequency of clockwise rotation, but except at the highest levels of CheY overproduction, clockwise rotation was abolished by depleting ATP. It is proposed that the CheY protein is normally in an inactive form and that ATP is required for formation of an active CheY* protein that binds to the switch on the flagellar motors and initiates clockwise rotation. Depletion of ATP partially inhibits feedback regulation of the cheB product, protein methylesterase, but this may reflect a second site of ATP action in chemotaxis.
Keilmann, A; Läßig, A K; Nospes, S
The definition of an auditory processing disorder (APD) is based on impairments of auditory functions. APDs are disturbances in processes central to hearing that cannot be explained by comorbidities such as attention deficit or language comprehension disorders. Symptoms include difficulties in differentiation and identification of changes in time, structure, frequency and intensity of sounds; problems with sound localization and lateralization, as well as poor speech comprehension in adverse listening environments and dichotic situations. According to the German definition of APD (as opposed to central auditory processing disorder, CAPD), peripheral hearing loss or cognitive impairment also exclude APD. The diagnostic methodology comprises auditory function tests and the required diagnosis of exclusion. APD is diagnosed if a patient's performance is two standard deviations below the normal mean in at least two areas of auditory processing. The treatment approach for an APD depends on the patient's particular deficits. Training, compensatory strategies and improvement of the listening conditions can all be effective.
Stock David W
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.
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. PMID:21118524
Pellegrinet, Luca; Rodilla, Veronica; Liu, Zhenyi; Chen, Shuang; Koch, Ute; Espinosa, Lluis; Kaestner, Klaus H; Kopan, Raphael; Lewis, Julian; Radtke, Freddy
Ablation of Notch signaling within the intestinal epithelium results in loss of proliferating crypt progenitors due to their conversion into postmitotic secretory cells. We aimed to confirm that Notch was active in stem cells (SCs), investigate consequences of loss of Notch signaling within the intestinal SC compartment, and identify the physiologic ligands of Notch in mouse intestine. Furthermore, we investigated whether the induction of goblet cell differentiation that results from loss of Notch requires the transcription factor Krüppel-like factor 4 (Klf4). Transgenic mice that carried a reporter of Notch1 activation were used for lineage tracing experiments. The in vivo functions of the Notch ligands Jagged1 (Jag1), Delta-like1 (Dll1), Delta-like4 (Dll4), and the transcription factor Klf4 were assessed in mice with inducible, gut-specific gene targeting (Vil-Cre-ER(T2)). Notch1 signaling was found to be activated in intestinal SCs. Although deletion of Jag1 or Dll4 did not perturb the intestinal epithelium, inactivation of Dll1 resulted in a moderate increase in number of goblet cells without noticeable effects of progenitor proliferation. However, simultaneous inactivation of Dll1 and Dll4 resulted in the complete conversion of proliferating progenitors into postmitotic goblet cells, concomitant with loss of SCs (Olfm4(+), Lgr5(+), and Ascl2(+)). Klf4 inactivation did not interfere with goblet cell differentiation in adult wild-type or in Notch pathway-deficient gut. Notch signaling in SCs and progenitors is activated by Dll1 and Dll4 ligands and is required for maintenance of intestinal progenitor and SCs. Klf4 is dispensable for goblet cell differentiation in intestines of adult Notch-deficient mice. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.
Pellegrinet, Luca; Rodilla, Veronica; Liu, Zhenyi; Chen, Shuang; Koch, Ute; Espinosa, Lluis; Kaestner, Klaus H.; Kopan, Raphael; Lewis, Julian; Radtke, Freddy
Background & Aims Ablation of Notch signaling within the intestinal epithelium results in loss of proliferating crypt progenitors, due to their conversion into post-mitotic secretory cells. We aimed to confirm that Notch was active in stem cells (SC), investigate consequences of loss of Notch signaling within the intestinal SC compartment, and identify the physiological ligands of Notch in mouse intestine. Furthermore, we investigated whether the induction of goblet cell differentiation that results from loss of Notch requires the transcription factor Krüppel-like factor 4 (Klf4). Methods Trasgenic mice that carried a reporter of Notch1 activation were used for lineage tracing experiments. The in vivo functions of the Notch ligands Jagged1 (Jag1), Delta-like1 (Dll1), Delta-like4 (Dll4), and the transcription factor Klf4 were assessed in mice with inducible, gut-specific gene targeting (Vil-Cre-ERT2). Results Notch1 signaling was found to be activated in intestinal SC. Although deletion of Jag1 or Dll4 did not perturb the intestinal epithelium, inactivation of Dll1 resulted in a moderate increase in number of goblet cells without noticeable effects of progenitor proliferation. However, simultaneous inactivation of Dll1 and Dll4 resulted in the complete conversion of proliferating progenitors into post-mitotic goblet cells, concomitant with loss of SC (Olfm4+, Lgr5+ and Ascl2+). Klf4 inactivation did not interfere with goblet cell differentiation in adult wild-type or in Notch pathway-deficient gut. Conclusions Notch signaling in SC and progenitors is activated by Dll1 and Dll4 ligands and is required for maintenance of intestinal progenitor and SC. Klf4 is dispensable for goblet cell differentiation in intestines of adult Notch-deficient mice. PMID:21238454
Full Text Available H z to 10 GH z Fig. 1. Radar signal processor (RSP) flow of operations purpose computer architectures . An abstract machine, in which only memory reads, writes, additions and multiplica- tions are considered to be significant operations..., is chosen for the model of computation. For each algorithm, a pseudo-code listing is used to find an expression for the required number of additions/subtractions, multiplications/divisions, as well as memory reads and writes. Based on the parameters...
Gutschalk, Alexander; Dykstra, Andrew R
Our auditory system is constantly faced with the task of decomposing the complex mixture of sound arriving at the ears into perceptually independent streams constituting accurate representations of individual sound sources. This decomposition, termed auditory scene analysis, is critical for both survival and communication, and is thought to underlie both speech and music perception. The neural underpinnings of auditory scene analysis have been studied utilizing invasive experiments with animal models as well as non-invasive (MEG, EEG, and fMRI) and invasive (intracranial EEG) studies conducted with human listeners. The present article reviews human neurophysiological research investigating the neural basis of auditory scene analysis, with emphasis on two classical paradigms termed streaming and informational masking. Other paradigms - such as the continuity illusion, mistuned harmonics, and multi-speaker environments - are briefly addressed thereafter. We conclude by discussing the emerging evidence for the role of auditory cortex in remapping incoming acoustic signals into a perceptual representation of auditory streams, which are then available for selective attention and further conscious processing. This article is part of a Special Issue entitled Human Auditory Neuroimaging. Copyright © 2013 Elsevier B.V. All rights reserved.
Heald, Shannon L. M.; Van Hedger, Stephen C.; Nusbaum, Howard C.
In our auditory environment, we rarely experience the exact acoustic waveform twice. This is especially true for communicative signals that have meaning for listeners. In speech and music, the acoustic signal changes as a function of the talker (or instrument), speaking (or playing) rate, and room acoustics, to name a few factors. Yet, despite this acoustic variability, we are able to recognize a sentence or melody as the same across various kinds of acoustic inputs and determine meaning based on listening goals, expectations, context, and experience. The recognition process relates acoustic signals to prior experience despite variability in signal-relevant and signal-irrelevant acoustic properties, some of which could be considered as “noise” in service of a recognition goal. However, some acoustic variability, if systematic, is lawful and can be exploited by listeners to aid in recognition. Perceivable changes in systematic variability can herald a need for listeners to reorganize perception and reorient their attention to more immediately signal-relevant cues. This view is not incorporated currently in many extant theories of auditory perception, which traditionally reduce psychological or neural representations of perceptual objects and the processes that act on them to static entities. While this reduction is likely done for the sake of empirical tractability, such a reduction may seriously distort the perceptual process to be modeled. We argue that perceptual representations, as well as the processes underlying perception, are dynamically determined by an interaction between the uncertainty of the auditory signal and constraints of context. This suggests that the process of auditory recognition is highly context-dependent in that the identity of a given auditory object may be intrinsically tied to its preceding context. To argue for the flexible neural and psychological updating of sound-to-meaning mappings across speech and music, we draw upon examples
Shannon L. M. Heald
Full Text Available In our auditory environment, we rarely experience the exact acoustic waveform twice. This is especially true for communicative signals that have meaning for listeners. In speech and music, the acoustic signal changes as a function of the talker (or instrument, speaking (or playing rate, and room acoustics, to name a few factors. Yet, despite this acoustic variability, we are able to recognize a sentence or melody as the same across various kinds of acoustic inputs and determine meaning based on listening goals, expectations, context, and experience. The recognition process relates acoustic signals to prior experience despite variability in signal-relevant and signal-irrelevant acoustic properties, some of which could be considered as “noise” in service of a recognition goal. However, some acoustic variability, if systematic, is lawful and can be exploited by listeners to aid in recognition. Perceivable changes in systematic variability can herald a need for listeners to reorganize perception and reorient their attention to more immediately signal-relevant cues. This view is not incorporated currently in many extant theories of auditory perception, which traditionally reduce psychological or neural representations of perceptual objects and the processes that act on them to static entities. While this reduction is likely done for the sake of empirical tractability, such a reduction may seriously distort the perceptual process to be modeled. We argue that perceptual representations, as well as the processes underlying perception, are dynamically determined by an interaction between the uncertainty of the auditory signal and constraints of context. This suggests that the process of auditory recognition is highly context-dependent in that the identity of a given auditory object may be intrinsically tied to its preceding context. To argue for the flexible neural and psychological updating of sound-to-meaning mappings across speech and music, we
Zurita-Martinez, Sara A; Puria, Rekha; Pan, Xuewen; Boeke, Jef D; Cardenas, Maria E
The Tor kinases regulate responses to nutrients and control cell growth. Unlike most organisms that only contain one Tor protein, Saccharomyces cerevisiae expresses two, Tor1 and Tor2, which are thought to share all of the rapamycin-sensitive functions attributable to Tor signaling. Here we conducted a genetic screen that defined the global TOR1 synthetic fitness or lethal interaction gene network. This screen identified mutations in distinctive functional categories that impaired vacuolar function, including components of the EGO/Gse and PAS complexes that reduce fitness. In addition, tor1 is lethal in combination with mutations in class C Vps complex components. We find that Tor1 does not regulate the known function of the class C Vps complex in protein sorting. Instead class C vps mutants fail to recover from rapamycin-induced growth arrest or to survive nitrogen starvation and have low levels of amino acids. Remarkably, addition of glutamate or glutamine restores viability to a tor1 pep3 mutant strain. We conclude that Tor1 is more effective than Tor2 at providing rapamycin-sensitive Tor signaling under conditions of amino acid limitation, and that an intact class C Vps complex is required to mediate intracellular amino acid homeostasis for efficient Tor signaling.
Green, Chad E; Pearson, David N; Christensen, Nadine B; Simon, Scott I
Cross-linking of L-selectin on leukocytes signals phosphorylation of mitogen-activated protein kinases (MAPKs) leading to activation of CD18 function and enhanced transmigration on inflamed endothelium. We examined how alterations in the topography of L-selectin correlate with the dynamics of CD18 activation and phosphorylation of MAPK. Simultaneous ligation of humanized antibodies DREG55 and DREG200 provided a strategy for regulating the extent of cross-linking. Triggering of CD11b/CD18 upregulation and adhesion required clustering of L-selectin to microvillus-sized patches of approximately 0.2 microm(2). Immunofluorescence revealed that L-selectin was colocalized with high-affinity CD18. Anti-L-selectin-coated protein A microspheres indicated that a single site of contact to a 5.5-microm bead, or multiple contacts to 0.94- or 0.3-microm beads, elicited maximum neutrophil activation. Adhesion signaled via L-selectin coincided with the kinetics of MAPK phosphorylation and was inhibited by blocking p38 or p42/44 activity. These data demonstrate the capacity of L-selectin to transduce signals effecting rapid ( approximately 1 s) neutrophil adhesion that is regulated by the size and frequency of receptor clustering.
Bulek, Katarzyna; Liu, Caini; Swaidani, Shadi; Wang, Liwen; Page, Richard C.; Gulen, Muhammet F.; Herjan, Tomasz; Abbadi, Amina; Qian, Wen; Sun, Dongxu; Lauer, Mark; Hascall, Vincent; Misra, Saurav; Chance, Mark; Aronica, Mark; Hamilton, Thomas; Li, Xiaoxia
Interleukin 17 (IL-17) plays a critical role in the pathogenesis of inflammatory and autoimmune diseases. Here we report that Act1, the key adaptor for IL-17R, forms a complex with IKKi upon IL-17 stimulation. Using IKKi-deficient mice, we show that IKKi was required for IL-17-induced inflammatory gene expression in primary airway epithelial cells, neutrophilia and pulmonary inflammation. IKKi deficiency abolished IL-17-induced Act1-TRAF2/5 complex formation, MAPK activation and mRNA stability, whereas the Act1-TRAF6-NFκB axis was retained. IKKi was required for IL-17-induced Act1 phosphorylation on serine 311, adjacent to a putative TRAF binding motif. S311A mutation impaired IL-17-mediated Act1-TRAF2/5 interaction and gene expression. Thus, IKKi is a novel kinase modulating IL-17 signaling through its impact on Act1 phosphorylation and consequent function. PMID:21822257
Chambers, Daniel B; Androschuk, Alaura; Rosenfelt, Cory; Langer, Steven; Harding, Mark; Bolduc, Francois V
Memory formation has been shown recently to be dependent on energy status in Drosophila. A well-established energy sensor is the insulin signaling (InS) pathway. Previous studies in various animal models including human have revealed the role of insulin levels in short-term memory but its role in long-term memory remains less clear. We therefore investigated genetically the spatial and temporal role of InS using the olfactory learning and long-term memory model in Drosophila. We found that InS is involved in both learning and memory. InS in the mushroom body is required for learning and long-term memory whereas long-term memory specifically is impaired after InS signaling disruption in the ellipsoid body, where it regulates the level of p70s6k, a downstream target of InS and a marker of protein synthesis. Finally, we show also that InS is acutely required for long-term memory formation in adult flies.
Ryan B Rountree
Full Text Available Articular cartilage plays an essential role in health and mobility, but is frequently damaged or lost in millions of people that develop arthritis. The molecular mechanisms that create and maintain this thin layer of cartilage that covers the surface of bones in joint regions are poorly understood, in part because tools to manipulate gene expression specifically in this tissue have not been available. Here we use regulatory information from the mouse Gdf5 gene (a bone morphogenetic protein [BMP] family member to develop new mouse lines that can be used to either activate or inactivate genes specifically in developing joints. Expression of Cre recombinase from Gdf5 bacterial artificial chromosome clones leads to specific activation or inactivation of floxed target genes in developing joints, including early joint interzones, adult articular cartilage, and the joint capsule. We have used this system to test the role of BMP receptor signaling in joint development. Mice with null mutations in Bmpr1a are known to die early in embryogenesis with multiple defects. However, combining a floxed Bmpr1a allele with the Gdf5-Cre driver bypasses this embryonic lethality, and leads to birth and postnatal development of mice missing the Bmpr1a gene in articular regions. Most joints in the body form normally in the absence of Bmpr1a receptor function. However, articular cartilage within the joints gradually wears away in receptor-deficient mice after birth in a process resembling human osteoarthritis. Gdf5-Cre mice provide a general system that can be used to test the role of genes in articular regions. BMP receptor signaling is required not only for early development and creation of multiple tissues, but also for ongoing maintenance of articular cartilage after birth. Genetic variation in the strength of BMP receptor signaling may be an important risk factor in human osteoarthritis, and treatments that mimic or augment BMP receptor signaling should be
Leerberg, Dena M; Sano, Kaori; Draper, Bruce W
The vertebrate ovary and testis develop from a sexually indifferent gonad. During early development of the organism, primordial germ cells (the gamete lineage) and somatic gonad cells coalesce and begin to undergo growth and morphogenesis to form this bipotential gonad. Although this aspect of development is requisite for a fertile adult, little is known about the genetic regulation of early gonadogenesis in any vertebrate. Here, we provide evidence that fibroblast growth factor (Fgf) signaling is required for the early growth phase of a vertebrate bipotential gonad. Based on mutational analysis in zebrafish, we show that the Fgf ligand 24 (Fgf24) is required for proliferation, differentiation, and morphogenesis of the early somatic gonad, and as a result, most fgf24 mutants are sterile as adults. Additionally, we describe the ultrastructural elements of the early zebrafish gonad and show that distinct somatic cell populations can be identified soon after the gonad forms. Specifically, we show that fgf24 is expressed in an epithelial population of early somatic gonad cells that surrounds an inner population of mesenchymal somatic gonad cells that are in direct contact with the germ cells, and that fgf24 is required for stratification of the somatic tissue. Furthermore, based on gene expression analysis, we find that differentiation of the inner mesenchymal somatic gonad cells into functional cell types in the larval and early juvenile-stage gonad is dependent on Fgf24 signaling. Finally, we argue that the role of Fgf24 in zebrafish is functionally analogous to the role of tetrapod FGF9 in early gonad development.
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
Budi, Erine H.; Patterson, Larissa B.; Parichy, David M.
SUMMARY Vertebrate pigment cells are derived from neural crest cells and are a useful system for studying neural crest-derived traits during post-embryonic development. In zebrafish, neural crest-derived melanophores differentiate during embryogenesis to produce stripes in the early larva. Dramatic changes to the pigment pattern occur subsequently during the larva-to-adult transformation, or metamorphosis. At this time, embryonic melanophores are replaced by newly differentiating metamorphic melanophores that form the adult stripes. Mutants with normal embryonic/early larval pigment patterns but defective adult patterns identify factors required uniquely to establish, maintain, or recruit the latent precursors to metamorphic melanophores. We show that one such mutant, picasso, lacks most metamorphic melanophores and results from mutations in the ErbB gene erbb3b, encoding an EGFR-like receptor tyrosine kinase. To identify critical periods for ErbB activities, we treated fish with pharmacological ErbB inhibitors and also knocked-down erbb3b by morpholino injection. These analyses reveal an embryonic critical period for ErbB signaling in promoting later pigment pattern metamorphosis, despite the normal patterning of embryonic/early larval melanophores. We further demonstrate a peak requirement during neural crest migration that correlates with early defects in neural crest pathfinding and peripheral ganglion formation. Finally, we show that erbb3b activities are both autonomous and non-autonomous to the metamorphic melanophore lineage. These data identify a very early, embryonic, requirement for erbb3b in the development of much later metamorphic melanophores, and suggest complex modes by which ErbB signals promote adult pigment pattern development. PMID:18508863
Jin Kwon Jeong
Full Text Available Recent studies on the anatomical and functional organization of GABAergic networks in central auditory circuits of the zebra finch have highlighted the strong impact of inhibitory mechanisms on both the central encoding and processing of acoustic information in a vocal learning species. Most of this work has focused on the caudomedial nidopallium (NCM, a forebrain area postulated to be the songbird analogue of the mammalian auditory association cortex. NCM houses neurons with selective responses to conspecific songs and is a site thought to house auditory memories required for vocal learning and, likely, individual identification. Here we review our recent work on the anatomical distribution of GABAergic cells in NCM, their engagement in response to song and the roles for inhibitory transmission in the physiology of NCM at rest and during the processing of natural communication signals. GABAergic cells are highly abundant in the songbird auditory forebrain and account for nearly half of the overall neuronal population in NCM with a large fraction of these neurons activated by song in freely-behaving animals. GABAergic synapses provide considerable local, tonic inhibition to NCM neurons at rest and, during sound processing, may contain the spread of excitation away from un-activated or quiescent parts of the network. Finally, we review our work showing that GABA A -mediated inhibition directly regulates the temporal organization of song-driven responses in awake songbirds, and appears to enhance the reliability of auditory encoding in NCM.
Jeong, Jin Kwon; Tremere, Liisa A; Ryave, Michael J; Vuong, Victor C; Pinaud, Raphael
Recent studies on the anatomical and functional organization of GABAergic networks in central auditory circuits of the zebra finch have highlighted the strong impact of inhibitory mechanisms on both the central encoding and processing of acoustic information in a vocal learning species. Most of this work has focused on the caudomedial nidopallium (NCM), a forebrain area postulated to be the songbird analogue of the mammalian auditory association cortex. NCM houses neurons with selective responses to conspecific songs and is a site thought to house auditory memories required for vocal learning and, likely, individual identification. Here we review our recent work on the anatomical distribution of GABAergic cells in NCM, their engagement in response to song and the roles for inhibitory transmission in the physiology of NCM at rest and during the processing of natural communication signals. GABAergic cells are highly abundant in the songbird auditory forebrain and account for nearly half of the overall neuronal population in NCM with a large fraction of these neurons activated by song in freely-behaving animals. GABAergic synapses provide considerable local, tonic inhibition to NCM neurons at rest and, during sound processing, may contain the spread of excitation away from un-activated or quiescent parts of the network. Finally, we review our work showing that GABA(A)-mediated inhibition directly regulates the temporal organization of song-driven responses in awake songbirds, and appears to enhance the reliability of auditory encoding in NCM.
Moradi, Shahram; Lidestam, Björn; Saremi, Amin; Rönnberg, Jerker
This study aimed to measure the initial portion of signal required for the correct identification of auditory speech stimuli (or isolation points, IPs) in silence and noise, and to investigate the relationships between auditory and cognitive functions in silence and noise. Twenty-one university students were presented with auditory stimuli in a gating paradigm for the identification of consonants, words, and final words in highly predictable and low predictable sentences. The Hearing in Noise Test (HINT), the reading span test, and the Paced Auditory Serial Attention Test were also administered to measure speech-in-noise ability, working memory and attentional capacities of the participants, respectively. The results showed that noise delayed the identification of consonants, words, and final words in highly predictable and low predictable sentences. HINT performance correlated with working memory and attentional capacities. In the noise condition, there were correlations between HINT performance, cognitive task performance, and the IPs of consonants and words. In the silent condition, there were no correlations between auditory and cognitive tasks. In conclusion, a combination of hearing-in-noise ability, working memory capacity, and attention capacity is needed for the early identification of consonants and words in noise.
Full Text Available Activation of the ErbB2 receptor tyrosine kinase stimulates breast cancer cell migration. Cell migration is a complex process that requires the synchronized reorganization of numerous subcellular structures including cell-to-matrix adhesions, the actin cytoskeleton and microtubules. How the multiple signaling pathways triggered by ErbB2 coordinate, in time and space, the various processes involved in cell motility, is poorly defined. We investigated the mechanism whereby ErbB2 controls microtubules and chemotaxis. We report that activation of ErbB2 increased both cell velocity and directed migration. Impairment of the Cdc42 and RhoA GTPases, but not of Rac1, prevented the chemotactic response. RhoA is a key component of the Memo/ACF7 pathway whereby ErbB2 controls microtubule capture at the leading edge. Upon Memo or ACF7 depletion, microtubules failed to reach the leading edge and cells lost their ability to follow the chemotactic gradient. Constitutive ACF7 targeting to the membrane in Memo-depleted cells reestablished directed migration. ErbB2-mediated activation of phospholipase C gamma (PLCγ also contributed to cell guidance. We further showed that PLCγ signaling, via classical protein kinases C, and Memo signaling converged towards a single pathway controlling the microtubule capture complex. Finally, inhibiting the PI3K/Akt pathway did not affect microtubule capture, but disturbed microtubule stability, which also resulted in defective chemotaxis. PI3K/Akt-dependent stabilization of microtubules involved repression of GSK3 activity on the one hand and inhibition of the microtubule destabilizing protein, Stathmin, on the other hand. Thus, ErbB2 triggers distinct and complementary pathways that tightly coordinate microtubule capture and microtubule stability to control chemotaxis.
Reisoli, Elisa; De Lucchini, Stefania; Nardi, Irma; Ori, Michela
Serotonin (5-HT) is a neuromodulator that plays many different roles in adult and embryonic life. Among the 5-HT receptors, 5-HT2B is one of the key mediators of 5-HT functions during development. We used Xenopus laevis as a model system to further investigate the role of 5-HT2B in embryogenesis, focusing on craniofacial development. By means of gene gain- and loss-of-function approaches and tissue transplantation assays, we demonstrated that 5-HT2B modulates, in a cell-autonomous manner, postmigratory skeletogenic cranial neural crest cell (NCC) behavior without altering early steps of cranial NCC development and migration. 5-HT2B overexpression induced the formation of an ectopic visceral skeletal element and altered the dorsoventral patterning of the branchial arches. Loss-of-function experiments revealed that 5-HT2B signaling is necessary for jaw joint formation and for shaping the mandibular arch skeletal elements. In particular, 5-HT2B signaling is required to define and sustain the Xbap expression necessary for jaw joint formation. To shed light on the molecular identity of the transduction pathway acting downstream of 5-HT2B, we analyzed the function of phospholipase C beta 3 (PLC) in Xenopus development and showed that PLC is the effector of 5-HT2B during craniofacial development. Our results unveiled an unsuspected role of 5-HT2B in craniofacial development and contribute to our understanding of the interactive network of patterning signals that is involved in the development and evolution of the vertebrate mandibular arch.
Garcia, Kevin; Delaux, Pierre-Marc; Cope, Kevin R; Ané, Jean-Michel
Ectomycorrhizal (ECM) symbioses are among the most widespread associations between roots of woody plants and soil fungi in forest ecosystems. These associations contribute significantly to the sustainability and sustainagility of these ecosystems through nutrient cycling and carbon sequestration. Unfortunately, the molecular mechanisms controlling the mutual recognition between both partners are still poorly understood. Elegant work has demonstrated that effector proteins from ECM and arbuscular mycorrhizal (AM) fungi regulate host defenses by manipulating plant hormonal pathways. In parallel, genetic and evolutionary studies in legumes showed that a 'common symbiosis pathway' is required for the establishment of the ancient AM symbiosis and has been recruited for the rhizobia-legume association. Given that genes of this pathway are present in many angiosperm trees that develop ectomycorrhizas, we propose their potential involvement in some but not all ECM associations. The maintenance of a successful long-term relationship seems strongly regulated by resource allocation between symbiotic partners, suggesting that nutrients themselves may serve as signals. This review summarizes our current knowledge on the early and late signal exchanges between woody plants and ECM fungi, and we suggest future directions for decoding the molecular basis of the underground dance between trees and their favorite fungal partners. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.
Osborne, Nick; Brand-Arzamendi, Koroboshka; Ober, Elke A.; Jin, Suk-Won; Verkade, Heather; Holtzman, Nathalia Glickman; Yelon, Deborah; Stainier, Didier Y.R.
Summary The bioactive lipid sphingosine 1-phosphate (S1P) and its G protein-coupled receptors play critical roles in cardiovascular, immune and neural development and function [1–6]. Despite its importance, many questions remain about S1P signaling, including how S1P, which is synthesized intracellularly, is released from cells. Mutations in the zebrafish gene encoding the S1P receptor Miles Apart (Mil)/S1P2 disrupt the formation of the primitive heart tube . We find that mutations of another zebrafish locus, two of hearts (toh), cause phenotypes that are morphologically indistinguishable from those seen in mil/s1p2 mutants. Positional cloning of toh reveals that it encodes a member of the Spinster-like family of putative transmembrane transporters. The biological functions of these proteins are poorly understood, although phenotypes of the Drosophila spinster and zebrafish not really started mutants suggest that these proteins may play a role in lipid trafficking [7, 8]. Through gain- and loss-of-function analyses, we show that toh is required for signaling by S1P2. Further evidence indicates that Toh is involved in the trafficking or cellular release of S1P. PMID:19062281
Osborne, Nick; Brand-Arzamendi, Koroboshka; Ober, Elke A; Jin, Suk-Won; Verkade, Heather; Holtzman, Nathalia Glickman; Yelon, Deborah; Stainier, Didier Y R
The bioactive lipid sphingosine 1-phosphate (S1P) and its G protein-coupled receptors play critical roles in cardiovascular, immunological, and neural development and function. Despite its importance, many questions remain about S1P signaling, including how S1P, which is synthesized intracellularly, is released from cells. Mutations in the zebrafish gene encoding the S1P receptor Miles Apart (Mil)/S1P(2) disrupt the formation of the primitive heart tube. We find that mutations of another zebrafish locus, two of hearts (toh), cause phenotypes that are morphologically indistinguishable from those seen in mil/s1p2 mutants. Positional cloning of toh reveals that it encodes a member of the Spinster-like family of putative transmembrane transporters. The biological functions of these proteins are poorly understood, although phenotypes of the Drosophila spinster and zebrafish not really started mutants suggest that these proteins may play a role in lipid trafficking. Through gain- and loss-of-function analyses, we show that toh is required for signaling by S1P(2). Further evidence indicates that Toh is involved in the trafficking or cellular release of S1P.
Dawes, Piers; Munro, Kevin J
It is widely recognized by hearing aid users and audiologists that a period of auditory acclimatization and adjustment is needed for new users to become accustomed to their devices. The aim of the present study was to test the idea that auditory acclimatization and adjustment to hearing aids involves a process of learning to "tune out" newly audible but undesirable sounds, which are described by new hearing aid users as annoying and distracting. It was hypothesized that (1) speech recognition thresholds in noise would improve over time for new hearing aid users, (2) distractibility to noise would reduce over time for new hearing aid users, (3) there would be a correlation between improved speech recognition in noise and reduced distractibility to background sounds, (4) improvements in speech recognition and distraction would be accompanied by self-report of reduced annoyance, and (5) improvements in speech recognition and distraction would be associated with higher general cognitive ability and more hearing aid use. New adult hearing aid users (n = 35) completed a test of aided speech recognition in noise (SIN) and a test of auditory distraction by background sound amplified by hearing aids on the day of fitting and 1, 7, 14, and 30 days post fitting. At day 30, participants completed self-ratings of the annoyance of amplified sounds. Daily hearing aid use was measured via hearing aid data logging, and cognitive ability was measured with the Wechsler Abbreviated Scale of Intelligence block design test. A control group of experienced hearing aid users (n = 20) completed the tests over a similar time frame. At day 30, there was no statistically significant improvement in SIN among new users versus experienced users. However, levels of hearing loss and hearing aid use varied widely among new users. A subset of new users with moderate hearing loss who wore their hearing aids at least 6 hr/day (n = 10) had significantly improved SIN (by ~3-dB signal to noise ratio
Lin, Gufa; Chen, Ying; Slack, Jonathan M W
The Xenopus tadpole has the capacity fully to regenerate its tail after amputation. Previously, we have established that this regeneration process requires the operation of several signaling pathways including the bone morphogenic protein, Wnt, and Fgf pathways. Here, we have addressed the signaling requirements for spinal cord and muscle regeneration in a tissue-specific manner. Two methods were used namely grafts of transgenic spinal cord to a wild type host, and the use of the Tet-on conditional transgenic system to express inhibitors in the individual tissues. For the grafting experiments, the tail was amputated through the graft, which contained a temperature inducible inhibitor of the Wnt-β-catenin pathway. For the Tet-on experiments, treatment with doxycycline was used to induce cell autonomous inhibitors of the Wnt-β-catenin or the Fgf pathway in either spinal cord or muscle. The results show that both spinal cord and muscle regeneration depend on both the Wnt-β-catenin and the Fgf pathways. This experimental design also enables us to observe the effect of inhibition of regeneration of one tissue on the regeneration of the others. Regardless of the method of inhibition, we find that reduction of spinal cord regeneration reduces regeneration of other parts of the tail, including the myotomal muscles. In contrast, reduction of muscle regeneration has no effect on the regeneration of the spinal cord. In common with other regeneration systems, this indicates that soluble factors from the spinal cord are needed to promote the regeneration of the other tissues in the tail. Copyright © 2012 Wiley Periodicals, Inc.
Fasanya, Bankole K
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.
Full Text Available Computational and experimental research has revealed that auditory sensory predictions are derived from regularities of the current environment by using internal generative models. However, so far, what has not been addressed is how the auditory system handles situations giving rise to redundant or even contradictory predictions derived from different sources of information. To this end, we measured error signals in the event-related brain potentials (ERPs in response to violations of auditory predictions. Sounds could be predicted on the basis of overall probability, i.e., one sound was presented frequently and another sound rarely. Furthermore, each sound was predicted by an informative visual cue. Participants' task was to use the cue and to discriminate the two sounds as fast as possible. Violations of the probability based prediction (i.e., a rare sound as well as violations of the visual-auditory prediction (i.e., an incongruent sound elicited error signals in the ERPs (Mismatch Negativity [MMN] and Incongruency Response [IR]. Particular error signals were observed even in case the overall probability and the visual symbol predicted different sounds. That is, the auditory system concurrently maintains and tests contradictory predictions. Moreover, if the same sound was predicted, we observed an additive error signal (scalp potential and primary current density equaling the sum of the specific error signals. Thus, the auditory system maintains and tolerates functionally independently represented redundant and contradictory predictions. We argue that the auditory system exploits all currently active regularities in order to optimally prepare for future events.
... auditory potentials; Brainstem auditory evoked potentials; Evoked response audiometry; Auditory brainstem response; ABR; BAEP ... Normal results vary. Results will depend on the person and the instruments used to perform the test.
Full Text Available Specific functional properties of dendritic cells (DCs have been suspected as being responsible for the impaired specific immune responses observed in human neonates. To analyze stimulatory requirements for the critical transition from immature, antigen-processing DCs to mature, antigen-presenting DCs, we investigated the effect of different proinflammatory mediators and antigens on phenotype and cytokine secretion of human neonatal DCs derived from hematopoietic progenitor cells (HPCs. Whereas single proinflammatory mediators were unable to induce the maturation of neonatal DCs, various combinations of IFNγ, CD40L, TNFα, LPS and antigens, induced the maturation of neonatal DCs documented by up-regulation of HLA-DR, CD83 and CD86. Combinations of proinflammatory mediators also increased cytokine secretion by neonatal DCs. Especially combined stimulation with LPS and IFNγ proved to be very efficient in inducing maturation and cytokine synthesis of neonatal DCs. In conclusion, neonatal DCs can be stimulated to express maturation as well as costimulatory surface molecules. However, induction of maturation requires combined stimulation with multiple proinflammatory signals.
Maharam, Edward; Yaport, Miguel; Villanueva, Nathaniel L; Akinyibi, Takintope; Laudier, Damien; He, Zhiyong; Leong, Daniel J; Sun, Hui B
Mesenchymal stem cell (MSC)-based treatments have shown promise for improving tendon healing and repair. MSCs have the potential to differentiate into multiple lineages in response to select chemical and physical stimuli, including into tenocytes. Cell elongation and cytoskeletal tension have been shown to be instrumental to the process of MSC differentiation. Previous studies have shown that inhibition of stress fiber formation leads MSCs to default toward an adipogenic lineage, which suggests that stress fibers are required for MSCs to sense the environmental factors that can induce differentiation into tenocytes. As the Rho/ROCK signal transduction pathway plays a critical role in both stress fiber formation and in cell sensation, we examined whether the activation of this pathway was required when inducing MSC tendon differentiation using rope-like silk scaffolds. To accomplish this, we employed a loss-of-function approach by knocking out ROCK, actin and myosin (two other components of the pathway) using the specific inhibitors Y-27632, Latrunculin A and blebbistatin, respectively. We demonstrated that independently disrupting the cytoskeleton and the Rho/ROCK pathway abolished the expression of tendon differentiation markers and led to a loss of spindle morphology. Together, these studies suggest that the tension that is generated by MSC elongation is essential for MSC teno-differentiation and that the Rho/ROCK pathway is a critical mediator of tendon differentiation on rope-like silk scaffolds.
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.
Cappe, Céline; Thut, Gregor; Romei, Vincenzo; Murray, Micah M
An object's motion relative to an observer can confer ethologically meaningful information. Approaching or looming stimuli can signal threats/collisions to be avoided or prey to be confronted, whereas receding stimuli can signal successful escape or failed pursuit. Using movement detection and subjective ratings, we investigated the multisensory integration of looming and receding auditory and visual information by humans. While prior research has demonstrated a perceptual bias for unisensory and more recently multisensory looming stimuli, none has investigated whether there is integration of looming signals between modalities. Our findings reveal selective integration of multisensory looming stimuli. Performance was significantly enhanced for looming stimuli over all other multisensory conditions. Contrasts with static multisensory conditions indicate that only multisensory looming stimuli resulted in facilitation beyond that induced by the sheer presence of auditory-visual stimuli. Controlling for variation in physical energy replicated the advantage for multisensory looming stimuli. Finally, only looming stimuli exhibited a negative linear relationship between enhancement indices for detection speed and for subjective ratings. Maximal detection speed was attained when motion perception was already robust under unisensory conditions. The preferential integration of multisensory looming stimuli highlights that complex ethologically salient stimuli likely require synergistic cooperation between existing principles of multisensory integration. A new conceptualization of the neurophysiologic mechanisms mediating real-world multisensory perceptions and action is therefore supported.
Brian N Pasley
Full Text Available How the human auditory system extracts perceptually relevant acoustic features of speech is unknown. To address this question, we used intracranial recordings from nonprimary auditory cortex in the human superior temporal gyrus to determine what acoustic information in speech sounds can be reconstructed from population neural activity. We found that slow and intermediate temporal fluctuations, such as those corresponding to syllable rate, were accurately reconstructed using a linear model based on the auditory spectrogram. However, reconstruction of fast temporal fluctuations, such as syllable onsets and offsets, required a nonlinear sound representation based on temporal modulation energy. Reconstruction accuracy was highest within the range of spectro-temporal fluctuations that have been found to be critical for speech intelligibility. The decoded speech representations allowed readout and identification of individual words directly from brain activity during single trial sound presentations. These findings reveal neural encoding mechanisms of speech acoustic parameters in higher order human auditory cortex.
Ye, Jianping; Hao, Zheng; Mumphrey, Michael B; Townsend, R Leigh; Patterson, Laurel M; Stylopoulos, Nicholas; Münzberg, Heike; Morrison, Christopher D; Drucker, Daniel J; Berthoud, Hans-Rudolf
Exaggerated GLP-1 and PYY secretion is thought to be a major mechanism in the reduced food intake and body weight after Roux-en-Y gastric bypass surgery. Here, we use complementary pharmacological and genetic loss-of-function approaches to test the role of increased signaling by these gut hormones in high-fat diet-induced obese rodents. Chronic brain infusion of a supramaximal dose of the selective GLP-1 receptor antagonist exendin-9-39 into the lateral cerebral ventricle significantly increased food intake and body weight in both RYGB and sham-operated rats, suggesting that, while contributing to the physiological control of food intake and body weight, central GLP-1 receptor signaling tone is not the critical mechanism uniquely responsible for the body weight-lowering effects of RYGB. Central infusion of the selective Y2R-antagonist BIIE0246 had no effect in either group, suggesting that it is not critical for the effects of RYGB on body weight under the conditions tested. In a recently established mouse model of RYGB that closely mimics surgery and weight loss dynamics in humans, obese GLP-1R-deficient mice lost the same amount of body weight and fat mass and maintained similarly lower body weight compared with wild-type mice. Together, the results surprisingly provide no support for important individual roles of either gut hormone in the specific mechanisms by which RYGB rats settle at a lower body weight. It is likely that the beneficial effects of bariatric surgeries are expressed through complex mechanisms that require combination approaches for their identification.
Christiansen, Claus Forup Corlin; Pedersen, Michael Syskind; Dau, Torsten
Classical speech intelligibility models, such as the speech transmission index (STI) and the speech intelligibility index (SII) are based on calculations on the physical acoustic signals. The present study predicts speech intelligibility by combining a psychoacoustically validated model of auditory...
Full Text Available If it is well known that knowledge facilitates higher cognitive functions, such as visual and auditory word recognition, little is known about the influence of knowledge on detection, particularly in the auditory modality. Our study tested the influence of phonological and lexical knowledge on auditory detection. Words, pseudo words and complex non phonological sounds, energetically matched as closely as possible, were presented at a range of presentation levels from sub threshold to clearly audible. The participants performed a detection task (Experiments 1 and 2 that was followed by a two alternative forced choice recognition task in Experiment 2. The results of this second task in Experiment 2 suggest a correct recognition of words in the absence of detection with a subjective threshold approach. In the detection task of both experiments, phonological stimuli (words and pseudo words were better detected than non phonological stimuli (complex sounds, presented close to the auditory threshold. This finding suggests an advantage of speech for signal detection. An additional advantage of words over pseudo words was observed in Experiment 2, suggesting that lexical knowledge could also improve auditory detection when listeners had to recognize the stimulus in a subsequent task. Two simulations of detection performance performed on the sound signals confirmed that the advantage of speech over non speech processing could not be attributed to energetic differences in the stimuli.
Maier, Esther C.; Whitfield, Tanya T.
During development of the zebrafish inner ear, regional patterning in the ventral half of the otic vesicle establishes zones of gene expression that correspond to neurogenic, sensory and non-neural cell fates. FGF and Retinoic acid (RA) signalling from surrounding tissues are known to have an early role in otic placode induction and otic axial patterning, but how external signalling cues are translated into intrinsic patterning during otic vesicle (OV) stages is not yet understood. FGF and RA signalling pathway members are expressed in and around the OV, suggesting important roles in later patterning or maintenance events. We have analysed the temporal requirement of FGF and RA signalling for otic development at stages after initial anteroposterior patterning has occurred. We show that high level FGF signalling acts to restrict sensory fates, whereas low levels favour sensory hair cell development; in addition, FGF is both required and sufficient to promote the expression of the non-neural marker otx1b in the OV. RA signalling has opposite roles: it promotes sensory fates, and restricts otx1b expression and the development of non-neural fates. This is surprisingly different from the earlier requirement for RA signalling in specification of non-neural fates via tbx1 expression, and highlights the shift in regulation that takes place between otic placode and vesicle stages in zebrafish. Both FGF and RA signalling are required for the development of the otic neurogenic domain and the generation of otic neuroblasts. In addition, our results indicate that FGF and RA signalling act in a feedback loop in the anterior OV, crucial for pattern refinement. PMID:25473832
Van Stry, Melanie; Kazlauskas, Andrius; Schreiber, Stuart L.; Symes, Karen
Platelet-derived growth factor receptor (PDGFR) signaling is essential for normal embryonic development in many organisms, including frog, mouse, zebrafish, and sea urchin. The mode of action of PDGFR signaling during early development is poorly understood, however, mostly because inhibition of signaling through either the PDGFRα or PDGFRβ is embryonic lethal. In Xenopus embryos, disruption of PDGFRα signaling causes migrating anterior mesoderm cells to lose direction and undergo apoptosis through the mitochondrial pathway. To understand the mechanism of PDGFRα function in this process, we have analyzed all known effector-binding sites in vivo. By using a chemical inducer of dimerization to activate chimera PDGFRαs, we have identified a role for phospholipase Cγ (PLCγ) in protecting cells from death. PDGFRα-mediated cell survival requires PLCγ and phosphatidylinositol 3-kinase signaling, and that PDGFRα with binding sites for these two signaling factors is sufficient for this activity. Other effectors of PDGFRα signaling, Shf, SHP-2, and Crk, are not required for this process. Thus, our findings show that PDGFRα signaling through PLCγ and phosphatidylinositol 3-kinase has a protective role in preventing apoptosis in early development. Furthermore, we demonstrate that small molecule inducers of dimerization provide a powerful system to manipulate receptor function in developing embryos. PMID:15919820
Van Stry, Melanie; Kazlauskas, Andrius; Schreiber, Stuart L; Symes, Karen
Platelet-derived growth factor receptor (PDGFR) signaling is essential for normal embryonic development in many organisms, including frog, mouse, zebrafish, and sea urchin. The mode of action of PDGFR signaling during early development is poorly understood, however, mostly because inhibition of signaling through either the PDGFRalpha or PDGFRbeta is embryonic lethal. In Xenopus embryos, disruption of PDGFRalpha signaling causes migrating anterior mesoderm cells to lose direction and undergo apoptosis through the mitochondrial pathway. To understand the mechanism of PDGFRalpha function in this process, we have analyzed all known effector-binding sites in vivo. By using a chemical inducer of dimerization to activate chimera PDGFRalphas, we have identified a role for phospholipase Cgamma (PLCgamma) in protecting cells from death. PDGFRalpha-mediated cell survival requires PLCgamma and phosphatidylinositol 3-kinase signaling, and that PDGFRalpha with binding sites for these two signaling factors is sufficient for this activity. Other effectors of PDGFRalpha signaling, Shf, SHP-2, and Crk, are not required for this process. Thus, our findings show that PDGFRalpha signaling through PLCgamma and phosphatidylinositol 3-kinase has a protective role in preventing apoptosis in early development. Furthermore, we demonstrate that small molecule inducers of dimerization provide a powerful system to manipulate receptor function in developing embryos.
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.
Pecenka, Nadine; Engel, Annerose; Keller, Peter E
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 of 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.
Schuel, Herbert; Burkman, Lani J; Lippes, Jack; Crickard, Kent; Mahony, Mary C; Giuffrida, Andrea; Picone, Robert P; Makriyannis, Alexandros
Ejaculated mammalian sperm require several hours exposure to secretions in female reproductive tracts, or incubation in appropriate culture medium in vitro, before acquiring the capacity to fertilize eggs. Arachidonylethanolamide (AEA), also known as anandamide, is a novel lipid-signal molecule that is an endogenous agonist (endocannabinoid) for cannabinoid receptors. We now report that AEA is present in human seminal plasma, mid-cycle oviductal fluid, and follicular fluid analyzed by high-performance liquid chromatography/mass spectrometry. Sperm are sequentially exposed to these reproductive fluids as they move from the vagina to the site of fertilization in the oviduct. Specific binding of the potent cannabinoid agonist [(3)H]CP-55,940 to human sperm was saturable (K(D) 9.71 +/- 1.04 nM), suggesting that they express cannabinoid receptors. R-methanandamide [AM-356], a potent and metabolically stable AEA analog, and (-)delta(9) tetrahydrocannabinol (THC), the major psychoactive constituent of Cannabis, modulated capacitation and fertilizing potential of human sperm in vitro. AM-356 elicited biphasic effects on the incidence of hyperactivated sperm motility (HA) between 1 and 6 hr of incubation: at (2.5 nM) it inhibited HA, while at (0.25 nM) it stimulated HA. Both AM-356 and THC inhibited morphological alterations over acrosomal caps between 2 and 6 hr (IC(50) 5.9 +/- 0.6 pM and 3.5 +/- 1.5 nM, respectively). Sperm fertilizing capacity, measured in the Hemizona Assay, was reduced 50% by (1 nM) AM-356. These findings suggest that AEA-signaling may regulate sperm functions required for fertilization in human reproductive tracts, and imply that smoking of marijuana could impact these processes. This study has potential medical and public policy ramifications because of the incidence of marijuana abuse by adults in our society, previously documented reproductive effects of marijuana, and the ongoing debate about medicinal use of marijuana and cannabinoids. Copyright
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...
Nikaido, Masataka; Navajas Acedo, Joaquin; Hatta, Kohei; Piotrowski, Tatjana
The lateral line system is a mechanosensory systems present in aquatic animals. The anterior and posterior lateral lines develop from anterior and posterior lateral line placodes (aLLp and pLLp), respectively. Although signaling molecules required for the induction of other cranial placodes have been well studied, the molecular mechanisms underlying formation of the lateral line placodes are unknown. In this study we tested the requirement of multiple signaling pathways, such as Wnt, Bmp Fgf, and Retinoic Acid for aLLp and pLLp induction. We determined that aLLp specification requires Fgf signaling, whilst pLLp specification requires retinoic acid which inhibits Fgf signaling. pLLp induction is also independent of Wnt and Bmp activities, even though these pathways limit the boundaries of the pLLp. This is the first report that the aLLp and pLLp depend on different inductive mechanisms and that pLLp induction requires the inhibition of Fgf, Wnt and Bmp signaling. Copyright © 2017 Elsevier Inc. All rights reserved.
Picton, T. W.; Hillyard, S. A.
Attention directed toward auditory stimuli, in order to detect an occasional fainter 'signal' stimulus, caused a substantial increase in the N1 (83 msec) and P2 (161 msec) components of the auditory evoked potential without any change in preceding components. This evidence shows that human auditory attention is not mediated by a peripheral gating mechanism. The evoked response to the detected signal stimulus also contained a large P3 (450 msec) wave that was topographically distinct from the preceding components. This late positive wave could also be recorded in response to a detected omitted stimulus in a regular train and therefore seemed to index a stimulus-independent perceptual decision process.
Fu, Guoping; Yu, Mei; Chen, Yuhong; Zheng, Yongwei; Zhu, Wen; Newman, Debra K; Wang, Demin; Wen, Renren
Pre-T cell receptor (TCR) signaling is required for pre-T cell survival, proliferation, and differentiation from the CD4 and CD8 double negative (DN) to the double positive (DP) stage. However, the pre-TCR signal transduction pathway is not fully understood and the signaling molecules involved have not been completely identified. Phospholipase Cγ (PLCγ) 1 is an important signaling molecule that generates two second messengers, diacylglycerol and inositol 1,4,5-trisphosphate, that are important to mediate PKC activation and intracellular Ca(2+) flux in many signaling pathways. Previously, we have shown that PLCγ1 is important for TCR-mediated signaling, development and T-cell activation, but the role of PLCγ1 in pre-TCR signal transduction and pre-T cell development is not known. In this study, we demonstrated that PLCγ1 expression level in pre-T cells was comparable to that in mature T cells. Deletion of PLCγ1 prior to the pre-TCR signaling stage partially blocked the DN3 to DN4 transition and reduced thymic cellularity. We also demonstrated that deletion of PLCγ1 impaired pre-T cell proliferation without affecting cell survival. Further study showed that deficiency of PLCγ1 impaired pre-TCR mediated Ca(2+) flux and Erk activation. Thus our studies demonstrate that PLCγ1 is important for pre-TCR mediated signal transduction and pre-T cell development. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Eyckmans, J; Roberts, S J; Schrooten, J; Luyten, F P
In this study, we investigated a clinically relevant model of in vivo ectopic bone formation utilizing human periosteum derived cells (HPDCs) seeded in a Collagraft carrier and explored the mechanisms by which this process is driven. Bone formation occurred after eight weeks when a minimum of one million HPDCs was loaded on Collagraft carriers and implanted subcutaneously in NMRI nu/nu mice. De novo bone matrix, mainly secreted by the HPDCs, was found juxta-proximal of the calcium phosphate (CaP) granules suggesting that CaP may have triggered the 'osteoinductive program'. Indeed, removal of the CaP granules by ethylenediaminetetraacetic acid decalcification prior to cell seeding and implantation resulted in loss of bone formation. In addition, inhibition of endogenous bone morphogenetic protein and Wnt signalling by overexpression of the secreted antagonists Noggin and Frzb, respectively, also abrogated osteoinduction. Proliferation of the engrafted HPDCs was strongly reduced in the decalcified scaffolds or when seeded with adenovirus-Noggin/Frzb transduced HPDCs indicating that cell division of the engrafted HPDCs is required for the direct bone formation cascade. These data suggest that this model of bone formation is similar to that observed during physiological intramembranous bone development and may be of importance when investigating tissue engineering strategies.
Full Text Available 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.
John Paul Christianson
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.
Fitzpatrick, Douglas C.; Roberts, Jason M.; Kuwada, Shigeyuki; Kim, Duck O.; Filipovic, Blagoje
Processing dynamic changes in the stimulus stream is a major task for sensory systems. In the auditory system, an increase in the temporal integration window between the inferior colliculus (IC) and auditory cortex is well known for monaural signals such as amplitude modulation, but a similar increase with binaural signals has not been demonstrated. To examine the limits of binaural temporal processing at these brain levels, we used the binaural beat stimulus, which causes a fluctuating inter...
Brown, Rachel M; Palmer, Caroline
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.
Kisiswa, Lilian; Erice, Clara; Ferron, Laurent; Wyatt, Sean; Osório, Catarina; Dolphin, Annette C; Davies, Alun M
Tumour necrosis factor receptor 1 (TNFR1)-activated TNFα reverse signalling, in which membrane-integrated TNFα functions as a receptor for TNFR1, enhances axon growth from developing sympathetic neurons and plays a crucial role in establishing sympathetic innervation. Here, we have investigated the link between TNFα reverse signalling and axon growth in cultured sympathetic neurons. TNFR1-activated TNFα reverse signalling promotes Ca(2+) influx, and highly selective T-type Ca(2+) channel inhibitors, but not pharmacological inhibitors of L-type, N-type and P/Q-type Ca(2+) channels, prevented enhanced axon growth. T-type Ca(2+) channel-specific inhibitors eliminated Ca(2+) spikes promoted by TNFα reverse signalling in axons and prevented enhanced axon growth when applied locally to axons, but not when applied to cell somata. Blocking action potential generation did not affect the effect of TNFα reverse signalling on axon growth, suggesting that propagated action potentials are not required for enhanced axon growth. TNFα reverse signalling enhanced protein kinase C (PKC) activation, and pharmacological inhibition of PKC prevented the axon growth response. These results suggest that TNFα reverse signalling promotes opening of T-type Ca(2+) channels along sympathetic axons, which is required for enhanced axon growth. © 2017 The Authors.
Full Text Available Abstract Background Sindbis viral vectors are able to efficiently target and kill tumor cells in vivo, as shown using pancreatic and ovarian cancer models. Infection results in apoptosis both in vitro and in vivo. Sindbis vector uptake is mediated by the LAMR, which is upregulated on a number of different tumor types, thus conferring specificity of the vector to a wide range of cancers. In this study we elucidate the mechanism of apoptosis in two tumor cell lines, MOSEC, derived from the ovarian epithelium and Pan02, derived from a pancreatic adenocarcinoma. A comprehensive understanding of the mechanism of apoptosis would facilitate the design of more effective vectors for cancer therapy. Results The initial phase of Sindbis vector induced apoptosis in MOSEC and Pan02 models reconfirms that viral infection is sensed by PKR due to double-stranded RNA intermediates associated with genomic replication. PKR activation results in translation inhibition through eIF2α phosphorylation and initiation of the stress response. Our studies indicate that the roles of two proteins, Mcl-1 and JNK, intimately link Sindbis induced translational arrest and cellular stress. Translational arrest inhibits the synthesis of anti-apoptotic Bcl-2 protein, Mcl-1. JNK activation triggers the release of Bad from 14-3-3, which ultimately results in apoptosis. These signals from translational arrest and cellular stress are propagated to the mitochondria where Bad and Bik bind to Bcl-xl and Mcl-1 respectively. Formation of these heterodimers displaces Bak, which results in caspase 9 cleavage and signaling through the mitochondrial pathway of apoptosis. Conclusion The host cell response to Sindbis is triggered through PKR activation. Our studies demonstrate that PKR activation and subsequent translational arrest is linked to both cellular stress and apoptosis. We have also found the linkage point between translational arrest and apoptosis to be Mcl-1, a protein whose constant
Sugden, Christopher; Ross, Susan; Annesley, Sarah J; Cole, Christian; Bloomfield, Gareth; Ivens, Alasdair; Skelton, Jason; Fisher, Paul R; Barton, Geoffrey; Williams, Jeffrey G
Dictyostelium is the only non-metazoan with functionally analyzed SH2 domains and studying them can give insights into their evolution and wider potential. LrrB has a novel domain configuration with leucine-rich repeat, 14-3-3 and SH2 protein-protein interaction modules. It is required for the correct expression of several specific genes in early development and here we characterize its role in later, multicellular development. During development in the light, slug formation in LrrB null (lrrB-) mutants is delayed relative to the parental strain, and the slugs are highly defective in phototaxis and thermotaxis. In the dark the mutant arrests development as an elongated mound, in a hitherto unreported process we term dark stalling. The developmental and phototaxis defects are cell autonomous and marker analysis shows that the pstO prestalk sub-region of the slug is aberrant in the lrrB- mutant. Expression profiling, by parallel micro-array and deep RNA sequence analyses, reveals many other alterations in prestalk-specific gene expression in lrrB- slugs, including reduced expression of the ecmB gene and elevated expression of ampA. During culmination ampA is ectopically expressed in the stalk, there is no expression of ampA and ecmB in the lower cup and the mutant fruiting bodies lack a basal disc. The basal disc cup derives from the pstB cells and this population is greatly reduced in the lrrB- mutant. This anatomical feature is a hallmark of mutants aberrant in signaling by DIF-1, the polyketide that induces prestalk and stalk cell differentiation. In a DIF-1 induction assay the lrrB- mutant is profoundly defective in ecmB activation but only marginally defective in ecmA induction. Thus the mutation partially uncouples these two inductive events. In early development LrrB interacts physically and functionally with CldA, another SH2 domain containing protein. However, the CldA null mutant does not phenocopy the lrrB- in its aberrant multicellular development or
Karina S Cramer
Full Text Available Glial cells, previously thought to have generally supporting roles in the central nervous system, are emerging as essential contributors to multiple aspects of neuronal circuit function and development. This review focuses on the contributions of glial cells to the development of specialized auditory pathways in the brainstem. These pathways display specialized synapses and an unusually high degree of precision in circuitry that enables sound source localization. The development of these pathways thus requires highly coordinated molecular and cellular mechanisms. Several classes of glial cells, including astrocytes, oligodendrocytes, and microglia, have now been explored in these circuits in both avian and mammalian brainstems. Distinct populations of astrocytes are found over the course of auditory brainstem maturation. Early appearing astrocytes are associated with spatial compartments in the avian auditory brainstem. Factors from late appearing astrocytes promote synaptogenesis and dendritic maturation, and astrocytes remain integral parts of specialized auditory synapses. Oligodendrocytes play a unique role in both birds and mammals in highly regulated myelination essential for proper timing to decipher interaural cues. Microglia arise early in brainstem development and may contribute to maturation of auditory pathways. Together these studies demonstrate the importance of non-neuronal cells in the assembly of specialized auditory brainstem circuits.
Kurosaka, Hiroshi; Trainor, Paul A.; Leroux-Berger, Margot; Iulianella, Angelo
Cranial nerves govern sensory and motor information exchange between the brain and tissues of the head and neck. The cranial nerves are derived from two specialized populations of cells, cranial neural crest cells and ectodermal placode cells. Defects in either cell type can result in cranial nerve developmental defects. Although several signaling pathways are known to regulate cranial nerve formation our understanding of how intercellular signaling between neural crest cells and placode cells is coordinated during cranial ganglia morphogenesis is poorly understood. Sonic Hedgehog (Shh) signaling is one key pathway that regulates multiple aspects of craniofacial development, but whether it co-ordinates cranial neural crest cell and placodal cell interactions during cranial ganglia formation remains unclear. In this study we examined a new Patched1 (Ptch1) loss-of-function mouse mutant and characterized the role of Ptch1 in regulating Shh signaling during cranial ganglia development. Ptch1Wig/ Wig mutants exhibit elevated Shh signaling in concert with disorganization of the trigeminal and facial nerves. Importantly, we discovered that enhanced Shh signaling suppressed canonical Wnt signaling in the cranial nerve region. This critically affected the survival and migration of cranial neural crest cells and the development of placodal cells as well as the integration between neural crest and placodes. Collectively, our findings highlight a novel and critical role for Shh signaling in cranial nerve development via the cross regulation of canonical Wnt signaling. PMID:25799573
Aanstad, Pia; Santos, Nicole; Corbit, Kevin C; Scherz, Paul J; Trinh, Le A; Salvenmoser, Willi; Huisken, Jan; Reiter, Jeremy F; Stainier, Didier Y R
Members of the Hedgehog (Hh) family of secreted proteins function as morphogens to pattern developing tissues and control cell proliferation. The seven-transmembrane domain (7TM) protein Smoothened (Smo) is essential for the activation of all levels of Hh signaling. However, the mechanisms by which Smo differentially activates low- or high-level Hh signaling are not known. Here we show that a newly identified mutation in the extracellular domain (ECD) of zebrafish Smo attenuates Smo signaling. The Smo agonist purmorphamine induces the stabilization, ciliary translocation, and high-level signaling of wild-type Smo. In contrast, purmorphamine induces the stabilization but not the ciliary translocation or high-level signaling of the Smo ECD mutant protein. Surprisingly, a truncated form of Smo that lacks the cysteine-rich domain of the ECD localizes to the cilium but is unable to activate high-level Hh signaling. We also present evidence that cilia may be required for Hh signaling in early zebrafish embryos. These data indicate that the ECD, previously thought to be dispensable for vertebrate Smo function, both regulates Smo ciliary localization and is essential for high-level Hh signaling.
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: email@example.com [Division of Applied Life Sciences (BK21), Graduate School of Gyeongsang National University, Jinju 660-701 (Korea, Republic of); Heo, Jae Bok, E-mail: firstname.lastname@example.org [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)
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.
Colak, D.; Mori, T.; Brill, M.S; Pfeifer, A.; Falk, S.; Deng, C.; Monteiro, R.; Mummery, C.L.; Sommer, L.; Gotz, M.
In the mammalian brain, neurogenesis continues only in few regions of the forebrain. The molecular signals governing neurogenesis in these unique neurogenic niches, however, are still ill defined. Here, we show that bone morphogenic protein (BMP)-mediated signaling is active in adult neural stem
Full Text Available Auditory integration training (AIT is a hearing enhancement training process for sensory input anomalies found in individuals with autism, attention deficit hyperactive disorder, dyslexia, hyperactivity, learning disability, language impairments, pervasive developmental disorder, central auditory processing disorder, attention deficit disorder, depressin, and hyperacute hearing. AIT, recently introduced in the United States, and has received much notice of late following the release of The Sound of a Moracle, by Annabel Stehli. In her book, Mrs. Stehli describes before and after auditory integration training experiences with her daughter, who was diagnosed at age four as having autism.
Full Text Available Auditory integration training (AIT is a hearing enhancement training process for sensory input anomalies found in individuals with autism, attention deficit hyperactive disorder, dyslexia, hyperactivity, learning disability, language impairments, pervasive developmental disorder, central auditory processing disorder, attention deficit disorder, depression, and hyper acute hearing. AIT, recently introduced in the United States, and has received much notice of late following the release of the sound of a miracle, by Annabel Stehli. In her book, Mrs. Stehli describes before and after auditory integration training experiences with her daughter, who was diagnosed at age four as having autism.
Lee, Hweeling; Noppeney, Uta
To form a coherent percept of the environment, the brain needs to bind sensory signals emanating from a common source, but to segregate those from different sources . Temporal correlations and synchrony act as prominent cues for multisensory integration [2-4], but the neural mechanisms by which such cues are identified remain unclear. Predictive coding suggests that the brain iteratively optimizes an internal model of its environment by minimizing the errors between its predictions and the sensory inputs [5,6]. This model enables the brain to predict the temporal evolution of natural audiovisual inputs and their statistical (for example, temporal) relationship. A prediction of this theory is that asynchronous audiovisual signals violating the model's predictions induce an error signal that depends on the directionality of the audiovisual asynchrony. As the visual system generates the dominant temporal predictions for visual leading asynchrony, the delayed auditory inputs are expected to generate a prediction error signal in the auditory system (and vice versa for auditory leading asynchrony). Using functional magnetic resonance imaging (fMRI), we measured participants' brain responses to synchronous, visual leading and auditory leading movies of speech, sinewave speech or music. In line with predictive coding, auditory leading asynchrony elicited a prediction error in visual cortices and visual leading asynchrony in auditory cortices. Our results reveal predictive coding as a generic mechanism to temporally bind signals from multiple senses into a coherent percept. Copyright © 2014 Elsevier Ltd. All rights reserved.
This paper aims to provide a review of the emerging Auditory Steady State Response in light of existing procedures for diagnosis of hearing loss in infants. Determining the type, degree, and configuration of hearing loss in infants is a challenge requiring sophisticated electrophysiological equipment of which Auditory ...
Lehmann, Gerlind U C; Berger, Sandra; Strauss, Johannes; Lehmann, Arne W; Pflüger, Hans-Joachim
Reduction of tympanal hearing organs is repeatedly found amongst insects and is associated with weakened selection for hearing. There is also an associated wing reduction, since flight is no longer required to evade bats. Wing reduction may also affect sound production. Here, the auditory system in four silent grasshopper species belonging to the Podismini is investigated. In this group, tympanal ears occur but sound signalling does not. The tympanal organs range from fully developed to remarkably reduced tympana. To evaluate the effects of tympanal regression on neuronal organisation and auditory sensitivity, the size of wings and tympana, sensory thresholds and sensory central projections are compared. Reduced tympanal size correlates with a higher auditory threshold. The threshold curves of all four species are tuned to low frequencies with a maximal sensitivity at 3-5 kHz. Central projections of the tympanal nerve show characteristics known from fully tympanate acridid species, so neural elements for tympanal hearing have been strongly conserved across these species. The results also confirm the correlation between reduction in auditory sensitivity and wing reduction. It is concluded that the auditory sensitivity of all four species may be maintained by stabilising selective forces, such as predation.
Baarsma, Hoeke A.; Menzen, Mark H.; Halayko, Andrew J.; Meurs, Herman; Kerstjens, Huib A. M.; Gosens, Reinoud
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:
Cai, Yixiao; Edin, Fredrik; Jin, Zhe; Alexsson, Andrei; Gudjonsson, Olafur; Liu, Wei; Rask-Andersen, Helge; Karlsson, Mikael; Li, Hao
Cochlear implants (CI) have been used for several decades to treat patients with profound hearing loss. Nevertheless, results vary between individuals, and fine hearing is generally poor due to the lack of discrete neural stimulation from the individual receptor hair cells. A major problem is the deliverance of independent stimulation signals to individual auditory neurons. Fine hearing requires significantly more stimulation contacts with intimate neuron/electrode interphases from ordered ax...
Masui, Kenta; Shibata, Noriyuki; Cavenee, Webster K; Mischel, Paul S
Mutations in growth factor receptor signaling pathways are common in cancer cells, including the highly lethal brain tumor glioblastoma (GBM) where they drive tumor growth through mechanisms including altering the uptake and utilization of nutrients. However, the impact of changes in micro-environmental nutrient levels on oncogenic signaling, tumor growth, and drug resistance is not well understood. We recently tested the hypothesis that external nutrients promote GBM growth and treatment resistance by maintaining the activity of mechanistic target of rapamycin complex 2 (mTORC2), a critical intermediate of growth factor receptor signaling, suggesting that altered cellular metabolism is not only a consequence of oncogenic signaling, but also potentially an important determinant of its activity. Here, we describe the studies that corroborate the hypothesis and propose others that derive from them. Notably, this line of reasoning raises the possibility that systemic metabolism may contribute to responsiveness to targeted cancer therapies. © 2016 WILEY Periodicals, Inc.
Chang, Baojun; Tessneer, Kandice L.; McManus, John; Liu, Xiaolei; Hahn, Scott; Pasula, Satish; Wu, Hao; Song, Hoogeun; Chen, Yiyuan; Cai, Xiaofeng; Dong, Yunzhou; Brophy, Megan L.; Rahman, Ruby; Ma, Jian-Xing; Xia, Lijun; Chen, Hong
Uncontrolled canonical Wnt signaling supports colon epithelial tumor expansion and malignant transformation. Understanding the regulatory mechanisms involved is crucial for elucidating the pathogenesis of and will provide new therapeutic targets for colon cancer. Epsins are ubiquitin-binding adaptor proteins upregulated in several human cancers; however, epsins’ involvement in colon cancer is unknown. Here we show that loss of intestinal epithelial epsins protects against colon cancer by significantly reducing the stability of the crucial Wnt signaling effector, dishevelled (Dvl2), and impairing Wnt signaling. Consistently, epsins and Dvl2 are correspondingly upregulated in colon cancer. Mechanistically, epsin binds Dvl2 via its epsin N-terminal homology domain and ubiquitin-interacting motifs and prohibits Dvl2 polyubiquitination and degradation. Our findings reveal an unconventional role for epsins in stabilizing Dvl2 and potentiating Wnt signaling in colon cancer cells to ensure robust colon cancer progression. Epsins’ pro-carcinogenic role suggests they are potential therapeutic targets to combat colon cancer. PMID:25871009
Workshop om erfaringer og brug af aktiverende metoder i undervisning i auditorier og på store hold. Hvilke metoder har fungeret godt og hvilke dårligt ? Hvilke overvejelser skal man gøre sig.......Workshop om erfaringer og brug af aktiverende metoder i undervisning i auditorier og på store hold. Hvilke metoder har fungeret godt og hvilke dårligt ? Hvilke overvejelser skal man gøre sig....
Teschendorff, Andrew E.; Banerji, Christopher R. S.; Severini, Simone; Kuehn, Reimer; Sollich, Peter
One of the key characteristics of cancer cells is an increased phenotypic plasticity, driven by underlying genetic and epigenetic perturbations. However, at a systems-level it is unclear how these perturbations give rise to the observed increased plasticity. Elucidating such systems-level principles is key for an improved understanding of cancer. Recently, it has been shown that signaling entropy, an overall measure of signaling pathway promiscuity, and computable from integrating a sample's gene expression profile with a protein interaction network, correlates with phenotypic plasticity and is increased in cancer compared to normal tissue. Here we develop a computational framework for studying the effects of network perturbations on signaling entropy. We demonstrate that the increased signaling entropy of cancer is driven by two factors: (i) the scale-free (or near scale-free) topology of the interaction network, and (ii) a subtle positive correlation between differential gene expression and node connectivity. Indeed, we show that if protein interaction networks were random graphs, described by Poisson degree distributions, that cancer would generally not exhibit an increased signaling entropy. In summary, this work exposes a deep connection between cancer, signaling entropy and interaction network topology. PMID:25919796
Gabriëls, Suzan H E J; Vossen, Jack H; Ekengren, Sophia K; van Ooijen, Gerben; Abd-El-Haliem, Ahmed M; van den Berg, Grardy C M; Rainey, Daphne Y; Martin, Gregory B; Takken, Frank L W; de Wit, Pierre J G M; Joosten, Matthieu H A J
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/Avr4-induced HR in Nicotiana benthamiana as demonstrated by virus-induced gene silencing (VIGS). The gene encodes a CC-NB-LRR type resistance (R) protein analogue that we have designated NRC1 (NB-LRR protein required for HR-associated cell death 1). Here we describe that knock-down of NRC1 in tomato not only affects the Cf-4/Avr4-induced HR but also compromises Cf-4-mediated resistance to C. fulvum. In addition, VIGS using NRC1 in N. benthamiana revealed that this protein is also required for the HR induced by the R proteins Cf-9, LeEix, Pto, Rx and Mi. Transient expression of NRC1(D481V), which encodes a constitutively active NRC1 mutant protein, triggers an elicitor-independent HR. Subsequently, we transiently expressed this auto-activating protein in N. benthamiana silenced for genes known to be involved in HR signalling, thereby allowing NRC1 to be positioned in an HR signalling pathway. We found that NRC1 requires RAR1 and SGT1 to be functional, whereas it does not require NDR1 and EDS1. As the Cf-4 protein requires EDS1 for its function, we hypothesize that NRC1 functions downstream of EDS1. We also found that NRC1 acts upstream of a MAP kinase pathway. We conclude that Cf-mediated resistance signalling requires a downstream NB-LRR protein that also functions in cell death signalling pathways triggered by other R proteins.
Wightman, Frederic L.; Jenison, Rick
All auditory sensory information is packaged in a pair of acoustical pressure waveforms, one at each ear. While there is obvious structure in these waveforms, that structure (temporal and spectral patterns) bears no simple relationship to the structure of the environmental objects that produced them. The properties of auditory objects and their layout in space must be derived completely from higher level processing of the peripheral input. This chapter begins with a discussion of the peculiarities of acoustical stimuli and how they are received by the human auditory system. A distinction is made between the ambient sound field and the effective stimulus to differentiate the perceptual distinctions among various simple classes of sound sources (ambient field) from the known perceptual consequences of the linear transformations of the sound wave from source to receiver (effective stimulus). Next, the definition of an auditory object is dealt with, specifically the question of how the various components of a sound stream become segregated into distinct auditory objects. The remainder of the chapter focuses on issues related to the spatial layout of auditory objects, both stationary and moving.
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
Di Salle, Francesco; Esposito, Fabrizio; Scarabino, Tommaso; Formisano, Elia; Marciano, Elio; Saulino, Claudio; Cirillo, Sossio; Elefante, Raffaele; Scheffler, Klaus; Seifritz, Erich
Functional magnetic resonance imaging (fMRI) has rapidly become the most widely used imaging method for studying brain functions in humans. This is a result of its extreme flexibility of use and of the astonishingly detailed spatial and temporal information it provides. Nevertheless, until very recently, the study of the auditory system has progressed at a considerably slower pace compared to other functional systems. Several factors have limited fMRI research in the auditory field, including some intrinsic features of auditory functional anatomy and some peculiar interactions between fMRI technique and audition. A well known difficulty arises from the high intensity acoustic noise produced by gradient switching in echo-planar imaging (EPI), as well as in other fMRI sequences more similar to conventional MR sequences. The acoustic noise interacts in an unpredictable way with the experimental stimuli both from a perceptual point of view and in the evoked hemodynamics. To overcome this problem, different approaches have been proposed recently that generally require careful tailoring of the experimental design and the fMRI methodology to the specific requirements posed by the auditory research. The novel methodological approaches can make the fMRI exploration of auditory processing much easier and more reliable, and thus may permit filling the gap with other fields of neuroscience research. As a result, some fundamental neural underpinnings of audition are being clarified, and the way sound stimuli are integrated in the auditory gestalt are beginning to be understood.
Brishna Soraya Kamal
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.
Brandstadter, Joshua D; Huang, Xiaopei; Yang, Yiping
NK cells are important for the control of vaccinia virus (VV) in vivo. Recent studies have shown that multiple pathways are required for effective activation of NK cells. These include both TLR-dependent and -independent pathways, as well as the NKG2D activating receptor that recognizes host stress-induced NKG2D ligands. However, it remains largely unknown what controls the upregulation of NKG2D ligands in response to VV infection. In this study using C57BL/6 mice, we first showed that IL-18 is critical for NK-cell activation and viral clearance. We then demonstrated that IL-18 signaling on both NK cells and DCs is required for efficient NK-cell activation upon VV infection in vitro. We further showed in vivo that efficient NK-cell activation in response to VV is dependent on DCs and IL-18 signaling in non-NK cells, suggesting an essential role for NK cell-extrinsic IL-18 signaling in NK-cell activation. Mechanistically, IL-18 signaling in DCs promotes expression of Rae-1, an NKG2D ligand. Collectively, our data reveal a previously unrecognized role for NK cell-extrinsic IL-18 signaling in NK-cell activation through upregulation of NKG2D ligands. These observations may provide insights into the design of effective NK-cell-based therapies for viral infections and cancer. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
McCourt, Mark E; Leone, Lynnette M
We asked whether the perceived direction of visual motion and contrast thresholds for motion discrimination are influenced by the concurrent motion of an auditory sound source. Visual motion stimuli were counterphasing Gabor patches, whose net motion energy was manipulated by adjusting the contrast of the leftward-moving and rightward-moving components. The presentation of these visual stimuli was paired with the simultaneous presentation of auditory stimuli, whose apparent motion in 3D auditory space (rightward, leftward, static, no sound) was manipulated using interaural time and intensity differences, and Doppler cues. In experiment 1, observers judged whether the Gabor visual stimulus appeared to move rightward or leftward. In experiment 2, contrast discrimination thresholds for detecting the interval containing unequal (rightward or leftward) visual motion energy were obtained under the same auditory conditions. Experiment 1 showed that the perceived direction of ambiguous visual motion is powerfully influenced by concurrent auditory motion, such that auditory motion 'captured' ambiguous visual motion. Experiment 2 showed that this interaction occurs at a sensory stage of processing as visual contrast discrimination thresholds (a criterion-free measure of sensitivity) were significantly elevated when paired with congruent auditory motion. These results suggest that auditory and visual motion signals are integrated and combined into a supramodal (audiovisual) representation of motion.
Bigelow, James; Ng, Chi-Wing; Poremba, Amy
Dorsal temporal pole (dTP) is a cortical region at the rostral end of the superior temporal gyrus that forms part of the ventral auditory object processing pathway. Anatomical connections with frontal and medial temporal areas, as well as a recent single-unit recording study, suggest this area may be an important part of the network underlying auditory working memory (WM). To further elucidate the role of dTP in auditory WM, local field potentials (LFPs) were recorded from the left dTP region of two rhesus macaques during an auditory delayed matching-to-sample (DMS) task. Sample and test sounds were separated by a 5-s retention interval, and a behavioral response was required only if the sounds were identical (match trials). Sensitivity of auditory evoked responses in dTP to behavioral significance and context was further tested by passively presenting the sounds used as auditory WM memoranda both before and after the DMS task. Average evoked potentials (AEPs) for all cue types and phases of the experiment comprised two small-amplitude early onset components (N20, P40), followed by two broad, large-amplitude components occupying the remainder of the stimulus period (N120, P300), after which a final set of components were observed following stimulus offset (N80OFF, P170OFF). During the DMS task, the peak amplitude and/or latency of several of these components depended on whether the sound was presented as the sample or test, and whether the test matched the sample. Significant differences were also observed among the DMS task and passive exposure conditions. Comparing memory-related effects in the LFP signal with those obtained in the spiking data raises the possibility some memory-related activity in dTP may be locally produced and actively generated. The results highlight the involvement of dTP in auditory stimulus identification and recognition and its sensitivity to the behavioral significance of sounds in different contexts. This article is part of a Special
Richard J Tunney
Full Text Available The butcher on the bus is a rhetorical device or hypothetical phenomenon that is often used to illustrate how recognition decisions can be based on different memory processes (Mandler, 1980. The phenomenon describes a scenario in which a person is recognized but the recognition is accompanied by a sense of familiarity or knowing characterised by an absence of contextual details such as the person’s identity. We report two recognition memory experiments that use signal detection analyses to determine whether this phenomenon is evidence for a recollection plus familiarity model of recognition or is better explained by a univariate signal detection model. We conclude that there is an interaction between confidence estimates and remember-know judgements that is not explained fully by either single process signal detection or traditional dual process models.
Shiotsuki, Ippei; Terao, Takeshi; Ishii, Nobuyoshi; Hatano, Koji
A 26-year-old female outpatient presenting with a depressive state suffered from auditory hallucinations at night. Her auditory hallucinations did not respond to blonanserin or paliperidone, but partially responded to risperidone. In view of the possibility that her auditory hallucinations began after starting trazodone, trazodone was discontinued, leading to a complete resolution of her auditory hallucinations. Furthermore, even after risperidone was decreased and discontinued, her auditory hallucinations did not recur. These findings suggest that trazodone may induce auditory hallucinations in some susceptible patients. PMID:24700048
Favrot, Sylvain Emmanuel
to 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...... environments (VAEs) with an array of loudspeakers. The LoRA system combines state-of-the-art acoustic room models with sound-field reproduction techniques. Limitations of these two techniques were taken into consideration together with the limitations of the human auditory system to localize sounds...
Hall, M.; Smeele, P.M.T.; Kuhl, P.K.
The integration of auditory and visual speech is observed when modes specify different places of articulation. Influences of auditory variation on integration were examined using consonant identifi-cation, plus quality and similarity ratings. Auditory identification predicted auditory-visual
Karunakaran, Smitha; Chowdhury, Ananya; Donato, Flavio; Quairiaux, Charles; Michel, Christoph M; Caroni, Pico
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.
Bates, Sarah H; Stearns, Walter H; Dundon, Trevor A; Schubert, Markus; Tso, Annette W K; Wang, Yongping; Banks, Alexander S; Lavery, Hugh J; Haq, Asma K; Maratos-Flier, Eleftheria; Neel, Benjamin G; Schwartz, Michael W; Myers, Martin G
Secretion of leptin from adipocytes communicates body energy status to the brain by activating the leptin receptor long form (LRb). LRb regulates energy homeostasis and neuroendocrine function; the absence of LRb in db/db mice results in obesity, impaired growth, infertility and diabetes. Tyr 1138 of LRb mediates activation of the transcription factor STAT3 during leptin action. To investigate the contribution of STAT3 signalling to leptin action in vivo, we replaced the gene encoding the leptin receptor (lepr) in mice with an allele coding for a replacement of Tyr 1138 in LRb with a serine residue (lepr(S1138)) that specifically disrupts the LRb-STAT3 signal. Here we show that, like db/db mice, lepr(S1138) homozygotes (s/s) are hyperphagic and obese. However, whereas db/db mice are infertile, short and diabetic, s/s mice are fertile, long and less hyperglycaemic. Furthermore, hypothalamic expression of neuropeptide Y (NPY) is elevated in db/db mice but not s/s mice, whereas the hypothalamic melanocortin system is suppressed in both db/db and s/s mice. LRb-STAT3 signalling thus mediates the effects of leptin on melanocortin production and body energy homeostasis, whereas distinct LRb signals regulate NPY and the control of fertility, growth and glucose homeostasis.
Magie, Craig R; Parkhurst, Susan M
The Rho small GTPase has been implicated in many cellular processes, including actin cytoskeletal regulation and transcriptional activation. The molecular mechanisms underlying Rho function in many of these processes are not yet clear. Here we report that in Drosophila, reduction of maternal Rho1 compromises signaling pathways consistent with defects in membrane trafficking events. These mutants fail to maintain expression of the segment polarity genes engrailed (en), wingless (wg), and hedgehog (hh), contributing to a segmentation phenotype. Formation of the Wg protein gradient involves the internalization of Wg into vesicles. The number of these Wg-containing vesicles is reduced in maternal Rho1 mutants, suggesting a defect in endocytosis. Consistent with this, stripes of cytoplasmic beta-catenin that accumulate in response to Wg signaling are narrower in these mutants relative to wild type. Additionally, the amount of extracellular Wg protein is reduced in maternal Rho1 mutants, indicating a defect in secretion. Signaling pathways downregulated by endocytosis, such as the epidermal growth factor receptor (EGFR) and Torso pathways, are hyperactivated in maternal Rho1 mutants, consistent with a general role for Rho1 in regulating signaling events governing proper patterning during Drosophila development.
Chang, Baojun; Tessneer, Kandice L; McManus, John; Liu, Xiaolei; Hahn, Scott; Pasula, Satish; Wu, Hao; Song, Hoogeun; Chen, Yiyuan; Cai, Xiaofeng; Dong, Yunzhou; Brophy, Megan L; Rahman, Ruby; Ma, Jian-Xing; Xia, Lijun; Chen, Hong
Uncontrolled canonical Wnt signalling supports colon epithelial tumour expansion and malignant transformation. Understanding the regulatory mechanisms involved is crucial for elucidating the pathogenesis of and will provide new therapeutic targets for colon cancer. Epsins are ubiquitin-binding adaptor proteins upregulated in several human cancers; however, the involvement of epsins in colon cancer is unknown. Here we show that loss of intestinal epithelial epsins protects against colon cancer by significantly reducing the stability of the crucial Wnt signalling effector, dishevelled (Dvl2), and impairing Wnt signalling. Consistently, epsins and Dvl2 are correspondingly upregulated in colon cancer. Mechanistically, epsin binds Dvl2 via its epsin N-terminal homology domain and ubiquitin-interacting motifs and prohibits Dvl2 polyubiquitination and degradation. Our findings reveal an unconventional role for epsins in stabilizing Dvl2 and potentiating Wnt signalling in colon cancer cells to ensure robust colon cancer progression. The pro-carcinogenic role of Epsins suggests that they are potential therapeutic targets to combat colon cancer.
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.
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,
Agerman, K; Canlon, B; Duan, M; Ernfors, P
Neurotrophic factors are secreted peptides that when interacting with specific classes of membrane receptors activate intracellular signaling cascades that prevents neuronal death during embryonic development. The establishment of gene-targeted null mutant mice for the neurotrophic factors, brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT3) has led to the discovery that they are crucial trophic factors for the survival of auditory and vestibular neurons during development. BDNF is the major survival factor for vestibular ganglion neurons, while NT-3 only support a small number of these neurons. In the cochlea, auditory type I neurons require NT3 for their survival, whereas type II neurons depend on BDNF. With this information at hand recent progress has been made regarding the prevention of aminoglycoside-induced hearing loss in the adult guinea pig. These results and the mechanisms leading to hair cell damage are discussed in this paper.
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
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.
Davy, Alice; Gale, Nicholas W.; Murray, Elizabeth W.; Klinghoffer, Richard A.; Soriano, Philippe; Feuerstein, Claude; Robbins, Stephen M.
Eph receptor tyrosine kinases and their corresponding surface-bound ligands, the ephrins, provide cues to the migration of cells and growth cones during embryonic development. Here we show that ephrin-A5, which is attached to the outer leaflet of the plasma membrane by a glycosyl-phosphatidylinositol-anchor, induces compartmentalized signaling within a caveolae-like membrane microdomain when bound to the extracellular domain of its cognate Eph receptor. The physiological response induced by this signaling event is concomitant with a change in the cellular architecture and adhesion of the ephrin-A5-expressing cells and requires the activity of the Fyn protein tyrosine kinase. This study stresses the relevance of bidirectional signaling involving the ephrins and Eph receptors during brain development. PMID:10601038
Airik, Rannar; Schueler, Markus; Airik, Merlin
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, ERC...
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; Sears, Rosalie C.; Clarke, Alan R.; Frame, Margaret C.; Sansom, Owen J.
SUMMARY 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 within the intestinal epithelium. Following Apc loss, FAK expression increased in a c-Myc-dependent manner. Codeletion of Apc and Fak strongly reduced proliferation normally induced following Apc loss, and this was associated with reduced levels of phospho-Akt and suppression of intestinal tumorigenesis in Apc heterozygous mice. Thus, FAK is required downstream of Wnt Signaling, for Akt/mTOR activation, intestinal regeneration, and tumorigenesis. Importantly, this work suggests that FAK inhibitors may suppress tumorigenesis in patients at high risk of developing colorectal cancer. PMID:20708588
Burmeister, Sabrina S
Mate choice is a decision making process with profound implication for the reproductive success of both the sender and the chooser. Preferences for conspecific over heterospecific males and for some conspecifics over others are typically mediated by a female's response to signals produced by males. And although one can experimentally describe a female's preference function, there is relatively little understood about the neural mechanisms mediating these preferences. In anurans, mating preferences have often been explained in terms of sensory biases. Indeed, in the túngara frog (Physalaemus pustulosus), the auditory system appears to act as a filter for conspecific calls. However, auditory responses are not good predictors of intraspecific mating preferences in túngara frogs. Rather, neural activity in the preoptic area, which can be gated by estradiol, is a better predictor of mating preferences. A similar pattern holds in spadefoot toads (Spea bombifrons): the preoptic area, but not the auditory midbrain, integrates physiological cues in its response to mating calls in a pattern that predicts preferences. Neuroanatomically, the anuran preoptic area is poised to mediate forebrain influences on auditory response of the midbrain and it has descending projections to the medulla and spinal cord that could directly influence motor responses. Indeed, lesions of the preoptic area abolish phonotaxis. A role for the preoptic area in mating preferences is supported by studies in mammals that show the preoptic area is required for the expression of preferences. Further, activity of the preoptic area correlates with mating preference in fish. This leads to a model for the neurobiological mechanisms of mate choice, in which sensory systems filter relevant signals from irrelevant ones, but the preoptic area assigns value to the range of relevant signals. © The Author 2017. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology
Orellana, Carlos Andrés Jurado; Pedersen, Christian Sejer; Møller, Henrik
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...... from previous studies suggests the filter bandwidth keeps decreasing below 100 Hz, although at a relatively lower rate than at higher frequencies. Main characteristics of the auditory filter were studied from below 100 Hz up to 1000 Hz. Center frequencies evaluated were 50, 63, 125, 250, 500, and 1000...... Hz. The notched-noise method was used, with the noise masker at 40 dB spectral density. A rounded exponential auditory filter model (roex(p,r)) was used to fit the masking data. Preliminary data on 1 subject is discussed. Considering the system as a whole (e.g. without removing the assumed middle...
Balic, Adam; Harcus, Yvonne M; Taylor, Matthew D; Brombacher, Frank; Maizels, Rick M
The requirement for IL-4 to promote differentiation of naive CD4(+) T cells into T(h)2 effector cell populations was established by classical in vitro studies. More recent in vivo data, however, indicate that signaling through the IL-4R is not essential for acquisition of the T(h)2 phenotype. In order to reconcile these seemingly contradictory conclusions, we have taken advantage of the ability of the excretory/secretory antigens of the gastrointestinal nematode Nippostrongylus brasiliensis to down-regulate T(h)1 cell development and drive T(h)2 cell expansion. We show that the initial development of IL-4-producing T cells is independent of IL-4R signaling but that the subsequent expansion of IL-4-producing CD4(+) T cells in a competitive environment that also contains T(h)1 potential is positively influenced by IL-4R signaling. We find that the production of IL-10 is the key IL-4R-dependent factor required to maintain T(h)2 dominance and that in the absence of IL-4R signaling, T(h)2 expansion can only be achieved by neutralization of T(h)1 cytokines. Moreover, in the absence of IL-4R signaling, reduced IL-10 production is due to the lack in expansion of an IL-10(+) T(h)2 population, rather than a global defect in the production of IL-10 by CD4(+) T cells. Thus, the evolution of T(h)2 dominance is achieved at the expense of T(h)1 cell development, normally restrained by IL-10 in an IL-4R-dependent manner. We conclude that T(h)2 cell development in response to N. brasiliensis antigen requires both IL-4 and IL-10 to act in concert on incipient populations of both T(h)1 and T(h)2 types.
Wild-Bode, Christine; Fellerer, Katrin; Kugler, Johanna; Haass, Christian; Capell, Anja
ADAM10 (a disintegrin and metalloprotease) initiates regulated intramembrane proteolysis by shedding the ectodomain of a number of different substrates. Shedding is followed by subsequent intramembrane proteolysis leading to the liberation of intracellular domains capable of nuclear signaling. ADAM10 substrates have been found at cell-cell contacts and are apparently involved in cell-cell interaction and cell migration. Here we have investigated the cellular mechanism that guides ADAM10 to substrates at cell-cell contacts. We demonstrate that intracellular trafficking of ADAM10 critically requires a novel sorting signal within its cytoplasmic domain. Sequential deletion of the cytoplasmic domain and site-directed mutagenesis suggest that a potential Src homology 3-binding domain is essential for ADAM10 sorting. In a polarized epithelial cell line this motif not only targets ADAM10 to adherens junctions but is also strictly required for ADAM10 function in E-cadherin processing and cell migration.
Fortin, Carl; Huang, Xiaopei; Yang, Yiping
NK cells play an important role in innate immune control of the infection with vaccinia virus (VV). However, it remains incompletely defined how the activation of NK cells in response to VV is regulated. In this study, we showed that STAT1 was critical for NK cell activation upon VV infection and the subsequent clearance of VV infection in vivo. We further demonstrated that STAT1 signaling in both NK and accessory cells such as dendritic cells was required for efficient NK cell activation upon VV infection. Mechanistically, STAT1 signaling in dendritic cells promoted the expression of NKG2D ligands, which is required for NK cell activation via the NKG2D pathway. Taken together, our data suggest that STAT1 mediates anti-VV effect by promoting NK cell activation through both NK-intrinsic and extrinsic mechanisms and may provide insights into the design of effective NK cell-based therapies for viral infections.
Ishii, A.; Fyffe-Maricich, S.L.; Furusho, M.; Miller, R.H.; Bansal, R.
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. Here we demonstrate a critical role for two important signaling molecules, extracelluar-signal-regulated-kinases-1 and -2 (ERK1/ERK2), downstream mediators of mitogen-activated protein kinases (MAPK), in the control of CNS myelin thickness. We generated and analyzed two lines of mice lacking both ERK1/ERK2 function specifically in oligodendrocyte-lineage cells. In the absence of ERK1/ERK2 signaling oligodendrocyte progenitor cells (OPC) proliferated and differentiated on schedule. Mutant oligodendrocytes also ensheathed axons normally and made a few wraps of compact myelin. However, the subsequent increase in myelination that correlated myelin thickness in proportion to the axon caliber failed to occur. Furthermore, although the numbers of differentiated oligodendrocytes in the adult mutants were unchanged, they showed an inability to upregulate the transcription of major myelin genes that normally occurs during active myelination. Similarly, in vitro ERK1/ERK2 deficient NG2+ oligodendrocytes differentiated normally but failed to form typical myelin-like membrane sheets. None of these effects were observed in single ERK1 or ERK2 mutants. These studies suggest that the predominant role of ERK1/ERK2 signaling in vivo is in promoting rapid myelin growth to increase its thickness, subsequent to oligodendrocyte differentiation and the initiation of myelination. PMID:22745486
Muraro, Daniele; Mellor, Nathan; Pound, Michael P; Help, Hanna; Lucas, Mikaël; Chopard, Jérôme; Byrne, Helen M; Godin, Christophe; Hodgman, T Charlie; King, John R; Pridmore, Tony P; Helariutta, Ykä; Bennett, Malcolm J; Bishopp, Anthony
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.
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.
Hosokawa, Ryoichi; Deng, Xuemei; Takamori, Kazunori; Xu, Xun; Urata, Mark; Bringas, Pablo; Chai, Yang
Reciprocal interactions between epithelium and mesenchyme are crucial for embryonic development. Fibroblast growth factors (FGFs) are a growth factor family that play an important role in epithelial-mesenchymal tissue interaction. We have generated epithelial-specific conditional knockout mice targeting Fibroblast growth factor receptor 2 (Fgfr2) to investigate the function of FGF signaling during craniofacial development. K14-Cre;Fgfr2(fl/fl) mice have skin defects, retarded tooth formation, and cleft palate. During the formation of the tooth primordium and palatal processes, cell proliferation in the epithelial cells of K14-Cre;Fgfr2(fl/fl) mice is reduced. Thus, FGF signaling via FGFR2 in the epithelium is crucial for cell proliferation activity during tooth and palate development. (c) 2009 Wiley-Liss, Inc.
Hines, D J; Schmitt, L I; Hines, R. M.; Moss, S.J.; Haydon, P.G.
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...
Dennis J Grab
Full Text Available 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.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.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.
Peiris, T Harshani; Ramirez, Daniel; Barghouth, Paul G; Oviedo, Néstor J
Akt (PKB) is a serine threonine protein kinase downstream of the phosphoinositide 3-kinase (PI3K) pathway. In mammals, Akt is ubiquitously expressed and is associated with regulation of cellular proliferation, metabolism, cell growth and cell death. Akt has been widely studied for its central role in physiology and disease, in particular cancer where it has become an attractive pharmacological target. However, the mechanisms by which Akt signaling regulates stem cell behavior in the complexity of the whole body are poorly understood. Planarians are flatworms with large populations of stem cells capable of dividing to support adult tissue renewal and regeneration. The planarian ortholog Smed-Akt is molecularly conserved providing unique opportunities to analyze the function of Akt during cellular turnover and repair of adult tissues. Our findings abrogating Smed-Akt with RNA-interference in the planarian Schmidtea mediterranea led to a gradual decrease in stem cell (neoblasts) numbers. The reduced neoblast numbers largely affected the maintenance of adult tissues including the nervous and excretory systems and ciliated structures in the ventral epithelia, which impaired planarian locomotion. Downregulation of Smed-Akt function also resulted in an increase of cell death throughout the animal. However, in response to amputation, levels of cell death were decreased and failed to localize near the injury site. Interestingly, the neoblast mitotic response was increased around the amputation area but the regenerative blastema failed to form. We demonstrate Akt signaling is essential for organismal physiology and in late stages of the Akt phenotype the reduction in neoblast numbers may impair regeneration in planarians. Functional disruption of Smed-Akt alters the balance between cell proliferation and cell death leading to systemic impairment of adult tissue renewal. Our results also reveal novel roles for Akt signaling during regeneration, specifically for the timely
Tobias Borra; Huib Versnel; Chantal Kemner; A. John van Opstal; Raymond van Ee
... tones. Current auditory models explain this phenomenon by a simple bandpass attention filter. Here, we demonstrate that auditory attention involves multiple pass-bands around octave-related frequencies above and below the cued tone...
Verhey, Jesko L; Ernst, Stephan M A; Yasin, Ifat
The present study was aimed at investigating the relationship between the mismatch negativity (MMN) and psychoacoustical effects of sequential streaming on comodulation masking release (CMR). The influence of sequential streaming on CMR was investigated using a psychoacoustical alternative forced-choice procedure and electroencephalography (EEG) for the same group of subjects. The psychoacoustical data showed, that adding precursors comprising of only off-signal-frequency maskers abolished the CMR. Complementary EEG data showed an MMN irrespective of the masker envelope correlation across frequency when only the off-signal-frequency masker components were present. The addition of such precursors promotes a separation of the on- and off-frequency masker components into distinct auditory objects preventing the auditory system from using comodulation as an additional cue. A frequency-specific adaptation changing the representation of the flanking bands in the streaming conditions may also contribute to the reduction of CMR in the stream conditions, however, it is unlikely that adaptation is the primary reason for the streaming effect. A neurophysiological correlate of sequential streaming was found in EEG data using MMN, but the magnitude of the MMN was not correlated with the audibility of the signal in CMR experiments. Dipole source analysis indicated different cortical regions involved in processing auditory streaming and modulation detection. In particular, neural sources for processing auditory streaming include cortical regions involved in decision-making. Copyright © 2012 Elsevier B.V. All rights reserved.
Pulupa, M.; Bale, S. D.; Bonnell, J. W.; Bowen, T. A.; Carruth, N.; Goetz, K.; Gordon, D.; Harvey, P. R.; Maksimovic, M.; Martínez-Oliveros, J. C.; Moncuquet, M.; Saint-Hilaire, P.; Seitz, D.; Sundkvist, D.
The Radio Frequency Spectrometer (RFS) is a two-channel digital receiver and spectrometer, which will make remote sensing observations of radio waves and in situ measurements of electrostatic and electromagnetic fluctuations in the solar wind. A part of the FIELDS suite for Solar Probe Plus (SPP), the RFS is optimized for measurements in the inner heliosphere, where solar radio bursts are more intense and the plasma frequency is higher compared to previous measurements at distances of 1 AU or greater. The inputs to the RFS receiver are the four electric antennas mounted near the front of the SPP spacecraft and a single axis of the SPP search coil magnetometer (SCM). Each RFS channel selects a monopole or dipole antenna input, or the SCM input, via multiplexers. The primary data products from the RFS are autospectra and cross spectra from the selected inputs. The spectra are calculated using a polyphase filter bank, which enables the measurement of low amplitude signals of interest in the presence of high-amplitude narrowband noise generated by spacecraft systems. We discuss the science signals of interest driving the RFS measurement objectives, describe the RFS analog design and digital signal processing, and show examples of current performance.
Tian, Hainan; Chen, Siyu; Yang, Wenting; Wang, Tianya; Zheng, Kaijie; Wang, Yating; Cheng, Yuxin; Zhang, Na; Liu, Shanda; Li, Dongqiu; Liu, Bao; Wang, Shucai
The plant hormone abscisic acid (ABA) plays a crucial role in regulating plant responses to environmental stresses. Interplay of several different proteins including the PYR/PYL/RCAR receptors, A-group PP2C protein phosphatases, SnRK2 protein kinases, and downstream transcription factors regulates ABA signalling. We report here the identification of a family of ABA-induced transcription repressors (AITRs) that act as feedback regulators in ABA signalling. We found that the expression of all the 6 Arabidopsis AITR genes was induced by exogenously ABA, and their expression levels were decreased in ABA biosynthesis mutant aba1-5. BLAST searches showed that AITRs are exclusively present in angiosperms. When recruited to the promoter region of a reporter gene by a fused DNA binding domain, all AITRs inhibited reporter gene expression in transfected protoplasts. In Arabidopsis, aitr mutants showed reduced sensitivity to ABA and to stresses such as salt and drought. Quantitative RT-PCR analysis demonstrated that the ABA-induced response of PP2C and some PYR/PYL/RCAR genes was reduced in AITR5 transgenic plants but increased in an aitr2 aitr5 aitr6 triple mutant. These results provide important new insights into the regulation of ABA signalling in plants, and such information may lead to the production of plants with enhanced resistance to environmental stresses. © 2017 John Wiley & Sons Ltd.
Full Text Available This study examines the impacts of directional and nondirectional auditory warning information in a collision warning system (CWS on driving behavior. The data on driving behavior is collected through experiment, with scenarios containing unexpected hazard events that include different warning content. As drivers approached the collision event, either a CWS auditory warning was given or no warning was given for a reference group. Discriminant analysis was used to investigate the relationship between directional auditory warning information and driving behavior. In the experiment, the CWS warnings significantly reduced brake reaction time and prompted drivers to press the brake pedal more heavily, demonstrating the effectiveness of CWS warnings in alerting drivers to avoid red-light running (RLR vehicles when approaching a signalized intersection. Providing a clear warning with directional information about an urgent hazard event could give drivers adequate time to prepare for the potential collision. In terms of deceleration, a directional information warning was shown to greatly help drivers react to critical events at signalized intersections with more moderate braking. From these results, requirements can be derived for the design of effective warning strategies for critical intersections.
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
Hou, JinChao; Chen, QiXing; Wu, XiaoLiang; Zhao, DongYan; Reuveni, Hadas; Licht, Tamar; Xu, MengLong; Hu, Hu; Hoeft, Andreas; Ben-Sasson, Shmuel A; Shu, Qiang; Fang, XiangMing
Efficient elimination of pathogenic bacteria is a critical determinant in the outcome of sepsis. Sphingosine-1-phosphate receptor 3 (S1PR3) mediates multiple aspects of the inflammatory response during sepsis, but whether S1PR3 signaling is necessary for eliminating the invading pathogens remains unknown. To investigate the role of S1PR3 in antibacterial immunity during sepsis. Loss- and gain-of-function experiments were performed using cell and murine models. S1PR3 levels were determined in patients with sepsis and healthy volunteers. S1PR3 protein levels were up-regulated in macrophages upon bacterial stimulation. S1pr3 -/- mice showed increased mortality and increased bacterial burden in multiple models of sepsis. The transfer of wild-type bone marrow-derived macrophages rescued S1pr3 -/- mice from lethal sepsis. S1PR3-overexpressing macrophages further ameliorated the mortality rate of sepsis. Loss of S1PR3 led to markedly decreased bacterial killing in macrophages. Enhancing endogenous S1PR3 activity using a peptide agonist potentiated the macrophage bactericidal function and improved survival rates in multiple models of sepsis. Mechanically, the reactive oxygen species levels were decreased and phagosome maturation was delayed in S1pr3 -/- macrophages due to impaired recruitment of vacuolar protein-sorting 34 to the phagosomes. In addition, S1RP3 expression levels were elevated in monocytes from patients with sepsis. Higher levels of monocytic S1PR3 were associated with efficient intracellular bactericidal activity, better immune status, and preferable outcomes. S1PR3 signaling drives bacterial killing and is essential for survival in bacterial sepsis. Interventions targeting S1PR3 signaling could have translational implications for manipulating the innate immune response to combat pathogens.
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.
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.
Tucker, Mark L; Yang, Ronghui
The stimulatory and inhibitory role of ethylene and auxin, respectively, in leaf abscission (leaf drop) is well documented. More recently, IDA (INFLORESCENCE DEFICIENT IN ABSCISSION) peptides and their putative interacting receptor-like-kinase partners, HAESA and HAESA-like2, were shown to be essential components in Arabidopsis floral organ abscission. Prior to research on IDA, it was reported that bean (Phaseolus vulgaris) leaf abscission required a diffusible signal that emanated from the vascular tissue. We were interested in determining whether the IDA signalling path might regulate abscission in plants other than Arabidopsis and whether IDA might act as a diffusible signal in abscission. Quantitative polymerase chain reaction was used to monitor gene expression and a GUS reporter gene construct used to determine the need for a diffusible signal in tomato. We identified 12 IDA-like and 11 HAESA-like genes in soybean (Glycine max) and monitored their gene expression in abscission in relation to the expression of several cell-wall-modifying proteins and aminocyclopropane-1-carboxylic acid synthases. Ethylene evoked the expression of several IDA-like genes in abscission zones (AZ), but also to a lesser degree in the adjacent petiole tissue. Surprisingly, IDA-like gene expression was very high in senescent soybean leaves. We identified five IDA-like genes in tomato (Solanum lycopersicum). Only one IDA-like gene was expressed in the tomato AZ and its expression was approximately equal in the AZ and petioles, but no IDA-like gene showed significant expression in leaves at up to 96 h of exposure to ethylene. IDA-like gene expression is up-regulated during soybean and tomato abscission but up-regulation was not limited to the AZ. Cell separation in the AZ cortex of tomato does not require a diffusible signal emanating from the stele. A role for IDA in soybean and tomato leaf abscission is discussed.
Suga, 1965), vocalization specific Peurons in squirrel monkeys (Newman and Wollberg, 1973a), song selective neurons in birds (Langner et al., 1981...191-205., 1990. Heffner, H.E. and Heffner, R.S. Effect of restricted cortical lesions on absolute thresholds and aphasia -like deficits in Japanese
de Boer, E.; Dreschler, W. A.
The study of audition has widened: Having been concentrated in the 1960s on a few topics like pitch perception, binaural hearing, and fatigue, it now spans many more subjects. In the present paper we have emphasized the following topics: frequency analysis--this topic includes spectral integration
Stähli, Alexandra Beatrice; Bosshardt, Dieter; Sculean, Anton; Gruber, Reinhard
Genome-wide microarrays have suggested that Emdogain regulates TGF-β target genes in gingival and palatal fibroblasts. However, definitive support for this contention and the extent to which TGF-β signaling contributes to the effects of Emdogain has remained elusive. We therefore studied the role of the TGF-β receptor I (TGF-βRI) kinase to mediate the effect of Emdogain on palatal fibroblasts. Palatal fibroblasts were exposed to Emdogain with and without the inhibitor for TGF-βRI kinase, SB43...
Froemke, Robert C; Martins, Ana Raquel O
The nervous system must dynamically represent sensory information in order for animals to perceive and operate within a complex, changing environment. Receptive field plasticity in the auditory cortex allows cortical networks to organize around salient features of the sensory environment during postnatal development, and then subsequently refine these representations depending on behavioral context later in life. Here we review the major features of auditory cortical receptive field plasticity in young and adult animals, focusing on modifications to frequency tuning of synaptic inputs. Alteration in the patterns of acoustic input, including sensory deprivation and tonal exposure, leads to rapid adjustments of excitatory and inhibitory strengths that collectively determine the suprathreshold tuning curves of cortical neurons. Long-term cortical plasticity also requires co-activation of subcortical neuromodulatory control nuclei such as the cholinergic nucleus basalis, particularly in adults. Regardless of developmental stage, regulation of inhibition seems to be a general mechanism by which changes in sensory experience and neuromodulatory state can remodel cortical receptive fields. We discuss recent findings suggesting that the microdynamics of synaptic receptive field plasticity unfold as a multi-phase set of distinct phenomena, initiated by disrupting the balance between excitation and inhibition, and eventually leading to wide-scale changes to many synapses throughout the cortex. These changes are coordinated to enhance the representations of newly-significant stimuli, possibly for improved signal processing and language learning in humans. Copyright © 2011 Elsevier B.V. All rights reserved.
Lerud, Karl D; Almonte, Felix V; Kim, Ji Chul; Large, Edward W
The auditory nervous system is highly nonlinear. Some nonlinear responses arise through active processes in the cochlea, while others may arise in neural populations of the cochlear nucleus, inferior colliculus and higher auditory areas. In humans, auditory brainstem recordings reveal nonlinear population responses to combinations of pure tones, and to musical intervals composed of complex tones. Yet the biophysical origin of central auditory nonlinearities, their signal processing properties, and their relationship to auditory perception remain largely unknown. Both stimulus components and nonlinear resonances are well represented in auditory brainstem nuclei due to neural phase-locking. Recently mode-locking, a generalization of phase-locking that implies an intrinsically nonlinear processing of sound, has been observed in mammalian auditory brainstem nuclei. Here we show that a canonical model of mode-locked neural oscillation predicts the complex nonlinear population responses to musical intervals that have been observed in the human brainstem. The model makes predictions about auditory signal processing and perception that are different from traditional delay-based models, and may provide insight into the nature of auditory population responses. We anticipate that the application of dynamical systems analysis will provide the starting point for generic models of auditory population dynamics, and lead to a deeper understanding of nonlinear auditory signal processing possibly arising in excitatory-inhibitory networks of the central auditory nervous system. This approach has the potential to link neural dynamics with the perception of pitch, music, and speech, and lead to dynamical models of auditory system development. Copyright © 2013 Elsevier B.V. All rights reserved.
Soranzo, Alessandro; Grassi, Massimo
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.
Full Text Available 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.
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.
Kwon, Hye-Joo, E-mail: email@example.com [Biology Department, Texas A& M University, College Station, TX77843-3258 (United States); Biology Department, Princess Nourah University, Riyadh 11671 (Saudi Arabia)
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. - Highlights: • VDR signaling is involved in embryonic heart development. • Knockdown of vdrb, but not vdra, causes decreased heart rate in zebrafish embryo. • Loss of vdr results in cardiac laterality defects. • Loss of vdra/b alters atrioventricular boundary formation. • Loss of vdra/b causes abnormal cardiac looping.
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.
Grouls, Stephan; Iglesias, Diana Margarita; Wentzensen, Nicolas; Moeller, Marcus Johannes; Bouchard, Maxime; Kemler, Rolf; Goodyer, Paul; Niggli, Felix; Gröne, Hermann-Josef; Kriz, Wilhelm; Koesters, Robert
β-Catenin/Wnt signaling is essential during early inductive stages of kidney development, but its role during postinductive stages of nephron development and maturation is not well understood. In this study, we used Pax8Cre mice to target β-catenin deficiency to renal epithelial cells at the late S-shaped body stage and the developing collecting ducts. The conditional β-catenin knockout mice formed abnormal kidneys and had reduced renal function. The kidneys were hypoplastic with a thin cortex; a superficial layer of tubules was missing. A high proportion of glomeruli had small, underdeveloped capillary tufts. In these glomeruli, well differentiated podocytes replaced parietal epithelial cells in Bowman's capsule; capillaries toward the outer aspect of these podocytes mimicked the formation of glomerular capillaries. Tracing nephrogenesis in embryonic conditional β-catenin knockout mice revealed that these "parietal podocytes" derived from precursor cells in the parietal layer of the S-shaped body by direct lineage switch. Taken together, these findings demonstrate that β-catenin/Wnt signaling is important during the late stages of nephrogenesis and for the lineage specification of parietal epithelial cells.
Ross, JM; Balasubramaniam, R.
© 2015, Springer-Verlag Berlin Heidelberg. The contributions of somatosensory, vestibular, and visual feedback to balance control are well documented, but the influence of auditory information, especially acoustic noise, on balance is less clear. Because somatosensory noise has been shown to reduce postural sway, we hypothesized that noise from the auditory modality might have a similar effect. Given that the nervous system uses noise to optimize signal transfer, adding mechanical or auditory...
Firszt, Jill B.; Reeder, Ruth M.; Holden, Timothy A.; Harold eBurton; Chole, Richard A.
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, ...
The subcortical auditory system is challenging to identify with standard human brain imaging techniques: MRI signal decreases toward the center of the brain as well as at higher resolution, both of which are necessary for imaging small brainstem auditory structures.Using high-resolution diffusion-weighted MRI, we asked:Can we identify auditory structures and connections in high-resolution ex vivo images?Which structures and connections can be mapped in vivo?
Full Text Available Abstract Introduction: It has been demonstrated that long-term Conductive Hearing Loss (CHL may influence the precise detection of the temporal features of acoustic signals or Auditory Temporal Processing (ATP. It can be argued that ATP may be the underlying component of many central auditory processing capabilities such as speech comprehension or sound localization. Little is known about the consequences of CHL on temporal aspects of central auditory processing. Objective: This study was designed to assess auditory temporal processing ability in individuals with chronic CHL. Methods: During this analytical cross-sectional study, 52 patients with mild to moderate chronic CHL and 52 normal-hearing listeners (control, aged between 18 and 45 year-old, were recruited. In order to evaluate auditory temporal processing, the Gaps-in-Noise (GIN test was used. The results obtained for each ear were analyzed based on the gap perception threshold and the percentage of correct responses. Results: The average of GIN thresholds was significantly smaller for the control group than for the CHL group for both ears (right: p = 0.004; left: p 0.05. Conclusion: The results suggest reduced auditory temporal processing ability in adults with CHL compared to normal hearing subjects. Therefore, developing a clinical protocol to evaluate auditory temporal processing in this population is recommended.
Kumar, Amit; Lualdi, Margaret; Lyozin, George T.; Sharma, Prashant; Loncarek, Jadranka; Fu, Xin-Yuan; Kuehn, Michael R.
In the early mouse embryo, a specialized population of extraembryonic visceral endoderm (VE) cells called the anterior VE (AVE) establishes the anterior posterior (AP) axis by restricting gastrulation-inducing signals to the opposite pole. These cells arise at the distal tip of the egg cylinder stage embryo and then asymmetrically migrate to the prospective anterior following the path of an earlier arising and migrating population called the distal VE (DVE). The Nodal-signaling pathway has been shown to have a critical role in the generation of the DVE and AVE and in their migration. The Nodal gene is expressed in both the VE and in the pluripotent epiblast, which gives rise to the germ layers. Previous findings have provided conflicting evidence as to the relative importance of Nodal signaling from the epiblast vs. VE for AP patterning. Here we show that conditional mutagenesis of the Nodal gene specifically within the VE leads to reduced Nodal expression levels in the epiblast and incomplete or failed AVE migration. These results support a required role for VE Nodal to maintain normal levels of expression in the epiblast, and suggest signaling from both VE and epiblast is important for AVE migration. PMID:25536399
Zimmerman, Sandra G; Thorpe, Lauren M; Medrano, Vilma R; Mallozzi, Carolyn A; McCartney, Brooke M
The tumor suppressor Adenomatous polyposis coli (APC) is a negative regulator of Wnt signaling and functions in cytoskeletal organization. Disruption of human APC in colonic epithelia initiates benign polyps that progress to carcinoma following additional mutations. The early events of polyposis are poorly understood, as is the role of canonical Wnt signaling in normal epithelial architecture and morphogenesis. To determine the consequences of complete loss of APC in a model epithelium, we generated APC2 APC1 double null clones in the Drosophila wing imaginal disc. APC loss leads to segregation, apical constriction, and invagination that result from transcriptional activation of canonical Wnt signaling. Further, we show that Wnt-dependent changes in cell fate can be decoupled from Wnt-dependent changes in cell shape. Wnt activation is reported to upregulate DE-cadherin in wing discs, and elevated DE-cadherin is thought to promote apical constriction. We find that apical constriction and invagination of APC null tissue are independent of DE-cadherin elevation, but are dependent on Myosin II activity. Further, we show that disruption of Rho1 suppresses apical constriction and invagination in APC null cells. Our data suggest a novel link between canonical Wnt signaling and epithelial structure that requires activation of the Rho1 pathway and Myosin II. Copyright 2010 Elsevier Inc. All rights reserved.
Zimmerman, Sandra G.; Thorpe, Lauren M.; Medrano, Vilma R.; Mallozzi, Carolyn A.; McCartney, Brooke M.
The tumor suppressor Adenomatous polyposis coli (APC) is a negative regulator of Wnt signaling and functions in cytoskeletal organization. Disruption of human APC in colonic epithelia initiates benign polyps that progress to carcinoma following additional mutations. The early events of polyposis are poorly understood, as is the role of canonical Wnt signaling in normal epithelial architecture and morphogenesis. To determine the consequences of complete loss of APC in a model epithelium, we generated APC2 APC1 double null clones in the Drosophila wing imaginal disc. APC loss leads to segregation, apical constriction, and invagination that result from transcriptional activation of canonical Wnt signaling. Further, we show that Wnt-dependent changes in cell fate can be decoupled from Wnt-dependent changes in cell shape. Wnt activation is reported to upregulate DE-cadherin in wing discs, and elevated DE-cadherin is thought to promote apical constriction. We find that apical constriction and invagination of APC null tissue are independent of DE-cadherin elevation, but are dependent on Myosin II activity. Further, we show that disruption of Rho1 suppresses apical constriction and invagination in APC null cells. Our data suggest a novel link between canonical Wnt signaling and epithelial structure that requires activation of the Rho1 pathway and Myosin II. PMID:20102708
Postigo, Antonio; Calella, Anna Maria; Fritzsch, Bernd; Knipper, Marlies; Katz, David; Eilers, Andreas; Schimmang, Thomas; Lewin, Gary R.; Klein, Rudiger; Minichiello, Liliana
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.
Full Text Available Embryonic neural crest cells contribute to the development of the craniofacial mesenchyme, forebrain meninges and perivascular cells. In this study, we investigated the function of ß-catenin signaling in neural crest cells abutting the dorsal forebrain during development. In the absence of ß-catenin signaling, neural crest cells failed to expand in the interhemispheric region and produced ectopic smooth muscle cells instead of generating dermal and calvarial mesenchyme. In contrast, constitutive expression of stabilized ß-catenin in neural crest cells increased the number of mesenchymal lineage precursors suggesting that ß-catenin signaling is necessary for the expansion of neural crest-derived mesenchymal cells. Interestingly, the loss of neural crest-derived mesenchymal stem cells (MSCs leads to failure of telencephalic midline invagination and causes ventricular system defects. This study shows that ß-catenin signaling is required for the switch of neural crest cells to MSCs and mediates the expansion of MSCs to drive the formation of mesenchymal structures of the head. Furthermore, loss of these structures causes striking defects in forebrain morphogenesis.
Gabay, Yafit; Dick, Frederic K; Zevin, Jason D; Holt, Lori L
Very little is known about how auditory categories are learned incidentally, without instructions to search for category-diagnostic dimensions, overt category decisions, or experimenter-provided feedback. This is an important gap because learning in the natural environment does not arise from explicit feedback and there is evidence that the learning systems engaged by traditional tasks are distinct from those recruited by incidental category learning. We examined incidental auditory category learning with a novel paradigm, the Systematic Multimodal Associations Reaction Time (SMART) task, in which participants rapidly detect and report the appearance of a visual target in 1 of 4 possible screen locations. Although the overt task is rapid visual detection, a brief sequence of sounds precedes each visual target. These sounds are drawn from 1 of 4 distinct sound categories that predict the location of the upcoming visual target. These many-to-one auditory-to-visuomotor correspondences support incidental auditory category learning. Participants incidentally learn categories of complex acoustic exemplars and generalize this learning to novel exemplars and tasks. Further, learning is facilitated when category exemplar variability is more tightly coupled to the visuomotor associations than when the same stimulus variability is experienced across trials. We relate these findings to phonetic category learning. (c) 2015 APA, all rights reserved).
Kaya, Emine Merve; Elhilali, Mounya
Sounds in everyday life seldom appear in isolation. Both humans and machines are constantly flooded with a cacophony of sounds that need to be sorted through and scoured for relevant information-a phenomenon referred to as the 'cocktail party problem'. A key component in parsing acoustic scenes is the role of attention, which mediates perception and behaviour by focusing both sensory and cognitive resources on pertinent information in the stimulus space. The current article provides a review of modelling studies of auditory attention. The review highlights how the term attention refers to a multitude of behavioural and cognitive processes that can shape sensory processing. Attention can be modulated by 'bottom-up' sensory-driven factors, as well as 'top-down' task-specific goals, expectations and learned schemas. Essentially, it acts as a selection process or processes that focus both sensory and cognitive resources on the most relevant events in the soundscape; with relevance being dictated by the stimulus itself (e.g. a loud explosion) or by a task at hand (e.g. listen to announcements in a busy airport). Recent computational models of auditory attention provide key insights into its role in facilitating perception in cluttered auditory scenes.This article is part of the themed issue 'Auditory and visual scene analysis'. © 2017 The Authors.
Mann, Philip H.; Suiter, Patricia A.
This teacher's guide contains a list of general auditory problem areas where students have the following problems: (a) inability to find or identify source of sound; (b) difficulty in discriminating sounds of words and letters; (c) difficulty with reproducing pitch, rhythm, and melody; (d) difficulty in selecting important from unimportant sounds;…
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.
Badenhorst, Paul; Xiao, Hua; Cherbas, Lucy; Kwon, So Yeon; Voas, Matt; Rebay, Ilaria; Cherbas, Peter; Wu, Carl
Drosophila NURF is an ISWI-containing ATP-dependent chromatin remodeling complex that regulates transcription by catalyzing nucleosome sliding. To determine in vivo gene targets of NURF, we performed whole genome expression analysis on mutants lacking the NURF-specific subunit NURF301. Strikingly, a large set of ecdysone-responsive targets is included among several hundred NURF-regulated genes. Null Nurf301 mutants do not undergo larval to pupal metamorphosis, and also enhance dominant-negative mutations in ecdysone receptor. Moreover, purified NURF binds EcR in an ecdysone-dependent manner, suggesting it is a direct effector of nuclear receptor activity. The conservation of NURF in mammals has broad implications for steroid signaling.
Williams, Kevin J.; Argus, Joseph P.; Zhu, Yue; Wilks, Moses Q.; Marbois, Beth N.; York, Autumn G.; Kidani, Yoko; Pourzia, Alexandra L.; Akhavan, David; Lisiero, Dominique N.; Komisopoulou, Evangelia; Henkin, Amy H.; Soto, Horacio; Chamberlain, Brian T.; Vergnes, Laurent; Jung, Michael E.; Torres, Jorge Z.; Liau, Linda M.; Christofk, Heather R.; Prins, Robert M.; Mischel, Paul S.; Reue, Karen; Graeber, Thomas G.; Bensinger, Steven J.
SREBPs are key transcriptional regulators of lipid metabolism and cellular growth. It has been proposed that SREBP signaling regulates cellular growth through its ability to drive lipid biosynthesis. Unexpectedly, we find that loss of SREBP activity inhibits cancer cell growth and viability by uncoupling fatty acid synthesis from desaturation. Integrated lipid profiling and metabolic flux analysis revealed that cancer cells with attenuated SREBP activity maintain long-chain saturated fatty acid synthesis, while losing fatty acid desaturation capacity. We traced this defect to the uncoupling of Fatty Acid Synthase activity from SCD1-mediated desaturation. This deficiency in desaturation drives an imbalance between the saturated and monounsaturated fatty acid pools resulting in severe lipotoxicity. Importantly, replenishing the monounsaturated fatty acid pool restored growth to SREBP-inhibited cells. These studies highlight the importance of fatty acid desaturation in cancer growth and provide a novel mechanistic explanation for the role of SREBPs in cancer metabolism. PMID:23440422
Sullivan, Kelly G; Levin, Michael
Neurotransmitters are not only involved in brain function but are also important signaling molecules for many diverse cell types. Neurotransmitters are widely conserved, from evolutionarily ancient organisms lacking nervous systems through man. Here, results are reported from a loss- and gain-of-function survey, using pharmacological modulators of several neurotransmitter pathways to examine possible roles for these pathways in normal embryogenesis. Applying reagents targeting the glutamatergic, adrenergic and dopaminergic pathways to embryos of Xenopus laevis from gastrulation to organogenesis stages, we observed and quantified numerous malformations, including craniofacial defects, hyperpigmentation, muscle mispatterning and miscoiling of the gut. These data implicate several key neurotransmitters in new embryonic patterning roles, reveal novel earlier stages for processes involved in eye development, suggest new targets for subsequent molecular-genetic investigation, and highlight the necessity for in-depth toxicology studies of psychoactive compounds to which human embryos might be exposed during pregnancy. © 2016 Anatomical Society.
Subhadeep Chatterjee; Christina Wistrom; Steven E. Lindow
...), is required to colonize insect vectors and to suppress virulence to grape. Here, we show that a hybrid two-component regulatory protein RpfC is involved in negative regulation of DSF synthesis by RpfF in X. fastidiosa. X...
Sussman, Elyse S.
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..
Mah, In Kyoung; Soloff, Rachel; Izuhara, Audrey K; Lakeland, Daniel L; Wang, Charles; Mariani, Francesca V
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. Copyright © 2016 Elsevier Inc. All rights reserved.
Lim, Hubert H.; Lenarz, Minoo; Lenarz, Thomas
The auditory midbrain implant (AMI) is a new hearing prosthesis designed for stimulation of the inferior colliculus in deaf patients who cannot sufficiently benefit from cochlear implants. The authors have begun clinical trials in which five patients have been implanted with a single shank AMI array (20 electrodes). The goal of this review is to summarize the development and research that has led to the translation of the AMI from a concept into the first patients. This study presents the rationale and design concept for the AMI as well a summary of the animal safety and feasibility studies that were required for clinical approval. The authors also present the initial surgical, psychophysical, and speech results from the first three implanted patients. Overall, the results have been encouraging in terms of the safety and functionality of the implant. All patients obtain improvements in hearing capabilities on a daily basis. However, performance varies dramatically across patients depending on the implant location within the midbrain with the best performer still not able to achieve open set speech perception without lip-reading cues. Stimulation of the auditory midbrain provides a wide range of level, spectral, and temporal cues, all of which are important for speech understanding, but they do not appear to sufficiently fuse together to enable open set speech perception with the currently used stimulation strategies. Finally, several issues and hypotheses for why current patients obtain limited speech perception along with several feasible solutions for improving AMI implementation are presented. PMID:19762428
Julstrom, Stephen; Kozma-Spytek, Linda
effect of possible noise-measurement weighting functions. The participants' preferred telephone speech levels subjectively matched or were somewhat lower than the level that they heard from a 65 dB SPL wideband reference. The mean speech (signal)-to-noise ratio requirement for them to consider their telephone experience "acceptable for normal use" was 20 dB, very similar to the results for the hearing aid users of the previous study. Significant differences in the participants' apparent levels of noise tolerance among the noise types when the noise level was determined using A-weighting were eliminated when a CI-specific noise-measurement weighting was applied. The results for the CI users in terms of both preferred levels for wireless and cordless phone communication and signal-to-noise requirements closely paralleled the corresponding results for hearing aid users from the previous study, and showed no significant differences between the microphone and telecoil modes of use. Signal-to-noise requirements were directly related to the participants' noise audibility threshold and were independent of noise type when appropriate noise-measurement weighting was applied. Extending the investigation to include noncontinuous interfering noises and forms of radiofrequency interference other than additive audiofrequency noise could be areas of future study. American Academy of Audiology.
Wang, Xin; Jung, Youn-Sang; Jun, Sohee; Lee, Sunhye; Wang, Wenqi; Schneider, Andrea; Sun Oh, Young; Lin, Steven H; Park, Bum-Joon; Chen, Junjie; Keyomarsi, Khandan; Park, Jae-Il
Cancer stem cells (CSCs) contribute to tumour heterogeneity, therapy resistance and metastasis. However, the regulatory mechanisms of cancer cell stemness remain elusive. Here we identify PCNA-associated factor (PAF) as a key molecule that controls cancer cell stemness. PAF is highly expressed in breast cancer cells but not in mammary epithelial cells (MECs). In MECs, ectopic expression of PAF induces anchorage-independent cell growth and breast CSC marker expression. In mouse models, conditional PAF expression induces mammary ductal hyperplasia. Moreover, PAF expression endows MECs with a self-renewing capacity and cell heterogeneity generation via Wnt signalling. Conversely, ablation of endogenous PAF induces the loss of breast cancer cell stemness. Further cancer drug repurposing approaches reveal that NVP-AUY922 downregulates PAF and decreases breast cancer cell stemness. Our results unveil an unsuspected role of the PAF-Wnt signalling axis in modulating cell plasticity, which is required for the maintenance of breast cancer cell stemness.
Yao, Shenqin; Bergan, Joseph; Lanjuin, Anne; Dulac, Catherine
The neural control of social behaviors in rodents requires the encoding of pheromonal cues by the vomeronasal system. Here we show that the typical preference of male mice for females is eliminated in mutants lacking oxytocin, a neuropeptide modulating social behaviors in many species. Ablation of the oxytocin receptor in aromatase-expressing neurons of the medial amygdala (MeA) fully recapitulates the elimination of female preference in males. Further, single-unit recording in the MeA uncove...
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.
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)
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.
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.
Wang, Liming; Yin, Jun; Nickles, Hannah T.; Ranke, Hannes; Tabuchi, Arata; Hoffmann, Julia; Tabeling, Christoph; Barbosa-Sicard, Eduardo; Chanson, Marc; Kwak, Brenda R.; Shin, Hee-Sup; Wu, Songwei; Isakson, Brant E.; Witzenrath, Martin; de Wit, Cor; Fleming, Ingrid; Kuppe, Hermann; Kuebler, Wolfgang M.
Hypoxic pulmonary vasoconstriction (HPV) is a physiological mechanism by which pulmonary arteries constrict in hypoxic lung areas in order to redirect blood flow to areas with greater oxygen supply. Both oxygen sensing and the contractile response are thought to be intrinsic to pulmonary arterial smooth muscle cells. Here we speculated that the ideal site for oxygen sensing might instead be at the alveolocapillary level, with subsequent retrograde propagation to upstream arterioles via connexin 40 (Cx40) endothelial gap junctions. HPV was largely attenuated by Cx40-specific and nonspecific gap junction uncouplers in the lungs of wild-type mice and in lungs from mice lacking Cx40 (Cx40–/–). In vivo, hypoxemia was more severe in Cx40–/– mice than in wild-type mice. Real-time fluorescence imaging revealed that hypoxia caused endothelial membrane depolarization in alveolar capillaries that propagated to upstream arterioles in wild-type, but not Cx40–/–, mice. Transformation of endothelial depolarization into vasoconstriction involved endothelial voltage-dependent α1G subtype Ca2+ channels, cytosolic phospholipase A2, and epoxyeicosatrienoic acids. Based on these data, we propose that HPV originates at the alveolocapillary level, from which the hypoxic signal is propagated as endothelial membrane depolarization to upstream arterioles in a Cx40-dependent manner. PMID:23093775
Full Text Available Genome-wide microarrays have suggested that Emdogain regulates TGF-β target genes in gingival and palatal fibroblasts. However, definitive support for this contention and the extent to which TGF-β signaling contributes to the effects of Emdogain has remained elusive. We therefore studied the role of the TGF-β receptor I (TGF-βRI kinase to mediate the effect of Emdogain on palatal fibroblasts. Palatal fibroblasts were exposed to Emdogain with and without the inhibitor for TGF-βRI kinase, SB431542. Emdogain caused 39 coding genes to be differentially expressed in palatal fibroblasts by microarray analysis (p10-fold. Importantly, in the presence of the TGF-βRI kinase inhibitor SB431542, Emdogain failed to cause any significant changes in gene expression. Consistent with this mechanism, three independent TGF-βRI kinase inhibitors and a TGF-β neutralizing antibody abrogated the increased expression of IL-11, a selected Emdogain target gene. The MAPK inhibitors SB203580 and U0126 lowered the impact of Emdogain on IL-11 expression. The data support that TGF-βRI kinase activity is necessary to mediate the effects of Emdogain on gene expression in vitro.
Stähli, Alexandra; Bosshardt, Dieter; Sculean, Anton; Gruber, Reinhard
Genome-wide microarrays have suggested that Emdogain regulates TGF-β target genes in gingival and palatal fibroblasts. However, definitive support for this contention and the extent to which TGF-β signaling contributes to the effects of Emdogain has remained elusive. We therefore studied the role of the TGF-β receptor I (TGF-βRI) kinase to mediate the effect of Emdogain on palatal fibroblasts. Palatal fibroblasts were exposed to Emdogain with and without the inhibitor for TGF-βRI kinase, SB431542. Emdogain caused 39 coding genes to be differentially expressed in palatal fibroblasts by microarray analysis (p10-fold). Importantly, in the presence of the TGF-βRI kinase inhibitor SB431542, Emdogain failed to cause any significant changes in gene expression. Consistent with this mechanism, three independent TGF-βRI kinase inhibitors and a TGF-β neutralizing antibody abrogated the increased expression of IL-11, a selected Emdogain target gene. The MAPK inhibitors SB203580 and U0126 lowered the impact of Emdogain on IL-11 expression. The data support that TGF-βRI kinase activity is necessary to mediate the effects of Emdogain on gene expression in vitro.
Baumann, Christian A.; Ribon, Vered; Kanzaki, Makoto; Thurmond, Debbie C.; Mora, Silvia; Shigematsu, Satoshi; Bickel, Perry E.; Pessin, Jeffrey E.; Saltiel, Alan R.
Insulin stimulates the transport of glucose into fat and muscle cells. Although the precise molecular mechanisms involved in this process remain uncertain, insulin initiates its actions by binding to its tyrosine kinase receptor, leading to the phosphorylation of intracellular substrates. One such substrate is the Cbl protooncogene product. Cbl is recruited to the insulin receptor by interaction with the adapter protein CAP, through one of three adjacent SH3 domains in the carboxy terminus of CAP. Upon phosphorylation of Cbl, the CAP-Cbl complex dissociates from the insulin receptor and moves to a caveolin-enriched, triton-insoluble membrane fraction. Here, to identify a molecular mechanism underlying this subcellular redistribution, we screened a yeast two-hybrid library using the amino-terminal region of CAP and identified the caveolar protein flotillin. Flotillin forms a ternary complex with CAP and Cbl, directing the localization of the CAP-Cbl complex to a lipid raft subdomain of the plasma membrane. Expression of the N-terminal domain of CAP in 3T3-L1 adipocytes blocks the stimulation of glucose transport by insulin, without affecting signalling events that depend on phosphatidylinositol-3-OH kinase. Thus, localization of the Cbl-CAP complex to lipid rafts generates a pathway that is crucial in the regulation of glucose uptake.
Hari M Bharadwaj
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
N. Jeremy Hill
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
Logan, Caitlin M; Rajakaruna, Suren; Bowen, Caitlin; Radice, Glenn L; Robinson, Michael L; Menko, A Sue
Tissue development and regeneration involve high-ordered morphogenetic processes that are governed by elements of the cytoskeleton in conjunction with cell adhesion molecules. Such processes are particularly important in the lens whose structure dictates its function. Studies of our lens-specific N-cadherin conditional knockout mouse (N-cadcKO) revealed an essential role for N-cadherin in the migration of the apical tips of differentiating lens fiber cells along the apical surfaces of the epithelium, a region termed the Epithelial Fiber Interface (EFI), that is necessary for normal fiber cell elongation and the morphogenesis. Studies of the N-cadcKO lens suggest that N-cadherin function in fiber cell morphogenesis is linked to the activation of Rac1 and myosin II, both signaling pathways central to the regulation of cell motility including determining the directionality of cellular movement. The absence of N-cadherin did not disrupt lateral contacts between fiber cells during development, and the maintenance of Aquaporin-0 and increased expression of EphA2 at cell-cell interfaces suggests that these molecules may function in this role. E-cadherin was maintained in newly differentiating fiber cells without interfering with expression of lens-specific differentiation proteins but was not able to replace N-cadherin function in these cells. The dependence of migration of the fiber cell apical domains along the EFI for lens morphogenesis on N-cadherin provides new insight into the process of tissue development. Copyright © 2017 Elsevier Inc. All rights reserved.
Treffy, Randall William; Collins, David; Hoshino, Natalia; Ton, Son; Katsevman, Gennadiy Aleksandrovich; Oleksiak, Michael; Runge, Elizabeth Marie; Cho, David; Russo, Matthew; Spec, Andrej; Gomulka, Jennifer; Henkemeyer, Mark; Rochlin, Michael William
The innervation of taste buds is an excellent model system for studying the guidance of axons during targeting because of their discrete nature and the high fidelity of innervation. The pregustatory epithelium of fungiform papillae is known to secrete diffusible axon guidance cues such as BDNF and Sema3A that attract and repel, respectively, geniculate ganglion axons during targeting, but diffusible factors alone are unlikely to explain how taste axon terminals are restricted to their territories within the taste bud. Nondiffusible cell surface proteins such as Ephs and ephrins can act as receptors and/or ligands for one another and are known to control axon terminal positioning in several parts of the nervous system, but they have not been studied in the gustatory system. We report that ephrin-B2 linked β-galactosidase staining and immunostaining was present along the dorsal epithelium of the mouse tongue as early as embryonic day 15.5 (E15.5), but was not detected at E14.5, when axons first enter the epithelium. Ephrin-B1 immunolabeling was barely detected in the epithelium and found at a somewhat higher concentration in the mesenchyme subjacent to the epithelium. EphB1 and EphB2 were detected in lingual sensory afferents in vivo and geniculate neurites in vitro. Ephrin-B1 and ephrin-B2 were similarly effective in repelling or suppressing outgrowth by geniculate neurites in vitro. These in vitro effects were independent of the neurotrophin used to promote outgrowth, but were reduced by elevated levels of laminin. In vivo, mice null for EphB1 and EphB2 exhibited decreased gustatory innervation of fungiform papillae. These data provide evidence that ephrin-B forward signaling is necessary for normal gustatory innervation of the mammalian tongue. © 2016 S. Karger AG, Basel.
Kelly-Laubscher, Roisin F; King, Jonathan C; Hacking, Damian; Somers, Sarin; Hastie, Samantha; Stewart, Tessa; Imamdin, Aqeela; Maarman, Gerald; Pedretti, Sarah; Lecour, Sandrine
Summary Aims Sphingosine-1-phosphate (S1P) is a cardioprotective agent. Signal transducer and activator of transcription 3 (STAT-3) is a key mediator of many cardioprotective agents. We aimed to explore whether STAT-3 is a key mediator in S1P-induced preconditioning. Methods Langendorff-perfused hearts from Wistar rats and wild-type or cardiomyocyte-specific STAT-3 knockout mice were pre-treated with S1P (10 nmol/l), with or without the STAT-3 pathway inhibitor AG490, before an ischaemia–reperfusion insult. Triphenyltetrazolium chloride and Evans blue staining were used for the determination of infarct size. Western blot analysis was carried out on the S1P pre-treated hearts for detection of cytosolic, nuclear and mitochondrial phosphorylated and total STAT-3 proteins. Results Pre-treatment with S1P decreased the infarct size in isolated rat (5 ± 3% vs control 26 ± 8%, p < 0.01) and wild-type mouse hearts (13 ± 1% vs control 33 ± 3%, p < 0.05). This protective effect was abolished in the rat hearts pre-treated with AG490 (30 ± 10%, p = ns vs control) and in the hearts from STAT-3 knockout mice (35 ± 4% vs control 30 ± 3%, p = ns). Levels of phosphorylated STAT-3 were significantly increased in both the nuclear (p < 0.05 vs control) and mitochondrial (p < 0.05 vs control) fractions in the S1P pre-treated hearts, but remained unchanged in the cytosolic fraction (p = ns vs control). Conclusion These novel results demonstrate that pharmacological preconditioning with S1P in the isolated heart is mediated by activation of mitochondrial and nuclear STAT-3, therefore suggesting that S1P may be a novel therapeutic target to modulate mitochondrial and nuclear function in cardiovascular disease in order to protect the heart against ischaemia–reperfusion. PMID:25000441
Singer, Bryan F; Neugebauer, Nichole M; Forneris, Justin; Rodvelt, Kelli R; Li, Dongdong; Bubula, Nancy; Vezina, Paul
Intermittent systemic exposure to psychostimulants leads to several forms of long-lasting behavioral plasticity including nonassociative sensitization and associative conditioning. In the nucleus accumbens (NAcc), the protein serine/threonine kinase cyclin-dependent kinase 5 (Cdk5) and its phosphorylation target, the guanine-nucleotide exchange factor kalirin-7 (Kal7), may contribute to the neuroadaptations underlying the formation of conditioned associations. Pharmacological inhibition of Cdk5 in the NAcc prevents the increases in dendritic spine density normally observed in this site following repeated cocaine. Mice lacking the Kal7 gene display similar effects. As increases in spine density may relate to the formation of associative memories and both Cdk5 and Kal7 regulate the generation of spines following repeated drug exposure, we hypothesized that either inhibiting Cdk5 or preventing its phosphorylation of Kal7 in the NAcc may prevent the induction of drug conditioning. In the present experiments, blockade in rats of NAcc Cdk5 activity with roscovitine (40 nmol/0.5 μl/side) prior to each of 4 injections of amphetamine (1.5 mg/kg; i.p.) prevented the accrual of contextual locomotor conditioning but spared the induction of locomotor sensitization as revealed on tests conducted one week later. Similarly, transient viral expression in the NAcc exclusively during amphetamine exposure of a threonine-alanine mutant form of Kal7 [mKal7(T1590A)] that is not phosphorylated by Cdk5 also prevented the accrual of contextual conditioning and spared the induction of sensitization. These results indicate that signaling via Cdk5 and Kal7 in the NAcc is necessary for the formation of context-drug associations, potentially through the modulation of dendritic spine dynamics in this site. Copyright © 2014 Elsevier Ltd. All rights reserved.
Dau, Torsten; Jepsen, Morten Løve; Ewert, Stephan D.
An auditory signal processing model is presented that simulates psychoacoustical data from a large variety of experimental conditions related to spectral and temporal masking. The model is based on the modulation filterbank model by Dau et al. [J. Acoust. Soc. Am. 102, 2892-2905 (1997)] but inclu......An auditory signal processing model is presented that simulates psychoacoustical data from a large variety of experimental conditions related to spectral and temporal masking. The model is based on the modulation filterbank model by Dau et al. [J. Acoust. Soc. Am. 102, 2892-2905 (1997...
Pickles, James O
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. © 2015 Elsevier B.V. All rights reserved.
Phan, Mimi L.; Vicario, David S.
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. PMID:25475353
Mohammad hosein Hekmat Ara
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.
Horie, Yoshinori; Toriizuka, Takashi
The focus of this study is a human's ability to make full use of listening and hearing. This ability consists of dividing auditory information into a signal and a noise. To evaluate the risk of using headphones, the study investigated the auditory perception when a warning sound is given in the presence of environmental noise.
Goll, Johanna C.; Kim, Lois G.; Hailstone, Julia C.; Lehmann, Manja; Buckley, Aisling; Crutch, Sebastian J.; Warren, Jason D.
The cognition of nonverbal sounds in dementia has been relatively little explored. Here we undertook a systematic study of nonverbal sound processing in patient groups with canonical dementia syndromes comprising clinically diagnosed typical amnestic Alzheimer's disease (AD; n = 21), progressive nonfluent aphasia (PNFA; n = 5), logopenic progressive aphasia (LPA; n = 7) and aphasia in association with a progranulin gene mutation (GAA; n = 1), and in healthy age-matched controls (n = 20). Based on a cognitive framework treating complex sounds as ‘auditory objects’, we designed a novel neuropsychological battery to probe auditory object cognition at early perceptual (sub-object), object representational (apperceptive) and semantic levels. All patients had assessments of peripheral hearing and general neuropsychological functions in addition to the experimental auditory battery. While a number of aspects of auditory object analysis were impaired across patient groups and were influenced by general executive (working memory) capacity, certain auditory deficits had some specificity for particular dementia syndromes. Patients with AD had a disproportionate deficit of auditory apperception but preserved timbre processing. Patients with PNFA had salient deficits of timbre and auditory semantic processing, but intact auditory size and apperceptive processing. Patients with LPA had a generalised auditory deficit that was influenced by working memory function. In contrast, the patient with GAA showed substantial preservation of auditory function, but a mild deficit of pitch direction processing and a more severe deficit of auditory apperception. The findings provide evidence for separable stages of auditory object analysis and separable profiles of impaired auditory object cognition in different dementia syndromes. PMID:21689671
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.
Jørgensen, Niklas Rye; Teilmann, Stefan Cuoni; Henriksen, Zanne
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......43 (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....
da Silva, Alexandre A; Spradley, Frank T; Granger, Joey P; Hall, John E; do Carmo, Jussara M
We previously demonstrated that leptin has powerful central nervous system (CNS)-mediated antidiabetic actions. In this study we tested the importance of melanocortin-4 receptors (MC4Rs) for leptin's ability to suppress food intake, increase blood pressure (BP) and heart rate (HR), and normalize glucose levels in insulin-dependent diabetes. MC4R knockout (MC4R-KO) and control wild-type (WT) rats were implanted with intracerebroventricular (ICV) cannula and BP and HR were measured 24 h/day by telemetry. After 5-day control period, an injection of streptozotocin (50 mg/kg, ip) was used to induce diabetes. Eight days after injection, an osmotic pump was implanted subcutaneously and connected to the ICV cannula to deliver leptin (15 μg/day) for 7 days. At baseline, MC4R-KO rats were hyperphagic and 40% heavier than WT rats. Despite obesity, BP was similar (112 ± 2 vs. 111 ± 2 mmHg) and HR was lower in MC4R-KO rats (320 ± 6 vs. 347 ± 5 beats/min). Induction of diabetes increased food intake (30%) and reduced BP (∼17 mmHg) and HR (∼61 beats/min) in WT rats, while food intake, BP, and HR were reduced by ∼10%, 7 mmHg, and 33 beats/min, respectively, in MC4R-KO rats. Leptin treatment normalized blood glucose (437 ± 10 to 136 ± 18 mg/dl), reduced food intake (40%), and increased HR (+60 beats/min) and BP (+9 mmHg) in WT rats. Only modest changes in blood glucose (367 ± 16 to 326 ± 23 mg/dl), food intake (5%), HR (+16 beats/min) and BP (+4 mmHg) were observed in MC4R-KO rats. These results indicate that intact CNS MC4R signaling is necessary for leptin to exert its chronic antidiabetic, anorexic, and cardiovascular actions. Copyright © 2015 the American Physiological Society.
Brandt, Jason; Bakker, Arnold; Maroof, David Aaron
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.
Skoe, Erika; Kraus, Nina
Musical training during childhood has been linked to more robust encoding of sound later in life. We take this as evidence for an auditory reserve: a mechanism by which individuals capitalize on earlier life experiences to promote auditory processing. We assert that early auditory experiences guide how the reserve develops and is maintained over the lifetime. Experiences that occur after childhood, or which are limited in nature, are theorized to affect the reserve, although their influence o...
De Groof, Geert; Poirier, Colline; George, Isabelle; Hausberger, Martine; Van der Linden, Annemie
Songbirds are an excellent model for investigating the perception of learned complex acoustic communication signals. Male European starlings (Sturnus vulgaris) sing throughout the year distinct types of song that bear either social or individual information. Although the relative importance of social and individual information changes seasonally, evidence of functional seasonal changes in neural response to these songs remains elusive. We thus decided to use in vivo functional magnetic resonance imaging (fMRI) to examine auditory responses of male starlings that were exposed to songs that convey different levels of information (species-specific and group identity or individual identity), both during (when mate recognition is particularly important) and outside the breeding season (when group recognition is particularly important). We report three main findings: (1) the auditory area caudomedial nidopallium (NCM), an auditory region that is analogous to the mammalian auditory cortex, is clearly involved in the processing/categorization of conspecific songs; (2) season-related change in differential song processing is limited to a caudal part of NCM; in the more rostral parts, songs bearing individual information induce higher BOLD responses than songs bearing species and group information, regardless of the season; (3) the differentiation between songs bearing species and group information and songs bearing individual information seems to be biased toward the right hemisphere. This study provides evidence that auditory processing of behaviorally-relevant (conspecific) communication signals changes seasonally, even when the spectro-temporal properties of these signals do not change. PMID:24391561
Mo, Y Y; Gross, D C
The syrB gene is required for syringomycin production by Pseudomonas syringae pv. syringae and full virulence during plant pathogenesis. Strain B3AR132 containing a syrB::lacZ fusion was used to detect transcriptional activation of the syrB gene in syringomycin minimal medium by plant metabolites with signal activity. Among 34 plant phenolic compounds tested, arbutin, phenyl-beta-D-glucopyranoside, and salicin were shown to be strong inducers of syrB, giving rise to approximately 1,200 U of beta-galactosidase activity at 100 microM; esculin and helicin were moderate inducers, with about 250 to 400 U of beta-galactosidase activity at 100 microM. Acetosyringone and flavonoids that serve as signal molecules in Agrobacterium and Rhizobium species, respectively, did not induce the syrB::lacZ fusion. All syrB inducers were phenolic glucosides and none of the aglucone derivatives were active, suggesting that the beta-glycosidic linkage was necessary for signal activity. Phenyl-beta-D-galactopyranoside containing galactose substituted for glucose in the beta-glycosidic linkage also lacked inducer activity. Phenolic signal activity was enhanced two- to fivefold by specific sugars common to plant tissues, including D-fructose, D-mannose, and sucrose. The effect of sugars on syrB induction was most noticeable at low concentrations of phenolic glucoside (i.e., 1 to 10 microM), indicating that sugars such as D-fructose increase the sensitivity of P. syringae pv. syringae to the phenolic plant signal. Besides induction of syrB, syringomycin biosynthesis by parental strain B3A-R was induced to yield over 250 U of toxin by the additions of arbutin and D-fructose to syringomycin minimal medium. These data indicate that syringomycin production by most strains of P. syringae pv. syringae is modulated by the perception of two classes of plant signal molecules and transduced to the transcriptional apparatus of syringomycin (syr) genes such as syrB. PMID:1885550
Gibson, Brett; Butler, William N; Taube, Jeffery S
Head-direction (HD) cells fire as a function of an animal's directional heading in the horizontal plane during two-dimensional navigational tasks . The information from HD cells is used with place and grid cells to form a spatial representation (cognitive map) of the environment [2, 3]. Previous studies have shown that when rats are inverted (upside down), they have difficulty learning a task that requires them to find an escape hole from one of four entry points but that they can learn it when released from one or two start points . Previous reports also indicate that the HD signal is disrupted when a rat is oriented upside down [5, 6]. Here we monitored HD cell activity in the two-entry-point version of the inverted task and when the rats were released from a novel start point. We found that despite the absence of direction-specific firing in HD cells when inverted, rats could successfully navigate to the escape hole when released from one of two familiar locations by using a habit-associated directional strategy. In the continued absence of normal HD cell activity, inverted rats failed to find the escape hole when started from a novel release point. The results suggest that the HD signal is critical for accurate navigation in situations that require a flexible allocentric cognitive mapping strategy, but not for situations that utilize habit-like associative spatial learning. Copyright © 2013 Elsevier Ltd. All rights reserved.
Leung, E; Xue, A; Wang, Y; Rougerie, P; Sharma, V P; Eddy, R; Cox, D; Condeelis, J
During metastasis to distant sites, tumor cells migrate to blood vessels. In vivo, breast tumor cells utilize a specialized mode of migration known as streaming, where a linear assembly of tumor cells migrate directionally towards blood vessels on fibronectin-collagen I-containing extracellular matrix (ECM) fibers in response to chemotactic signals. We have successfully reconstructed tumor cell streaming in vitro by co-plating tumors cells, macrophages and endothelial cells on 2.5 μm thick ECM-coated micro-patterned substrates. We found that tumor cells and macrophages, when plated together on the micro-patterned substrates, do not demonstrate sustained directional migration in only one direction (sustained directionality) but show random bi-directional walking. Sustained directionality of tumor cells as seen in vivo was established in vitro when beads coated with human umbilical vein endothelial cells were placed at one end of the micro-patterned 'ECM fibers' within the assay. We demonstrated that these endothelial cells supply the hepatocyte growth factor (HGF) required for the chemotactic gradient responsible for sustained directionality. Using this in vitro reconstituted streaming system, we found that directional streaming is dependent on, and most effectively blocked, by inhibiting the HGF/C-Met signaling pathway between endothelial cells and tumor cells. Key observations made with the in vitro reconstituted system implicating C-Met signaling were confirmed in vivo in mammary tumors using the in vivo invasion assay and intravital multiphoton imaging of tumor cell streaming. These results establish HGF/C-Met as a central organizing signal in blood vessel-directed tumor cell migration in vivo and highlight a promising role for C-Met inhibitors in blocking tumor cell streaming and metastasis in vivo, and for use in human trials.
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.
Quam, Rolf; Martínez, Ignacio; Rosa, Manuel; Bonmatí, Alejandro; Lorenzo, Carlos; de Ruiter, Darryl J; Moggi-Cecchi, Jacopo; Conde Valverde, Mercedes; Jarabo, Pilar; Menter, Colin G; Thackeray, J Francis; Arsuaga, Juan Luis
Studies of sensory capacities in past life forms have offered new insights into their adaptations and lifeways. Audition is particularly amenable to study in fossils because it is strongly related to physical properties that can be approached through their skeletal structures. We have studied the anatomy of the outer and middle ear in the early hominin taxa Australopithecus africanus and Paranthropus robustus and estimated their auditory capacities. Compared with chimpanzees, the early hominin taxa are derived toward modern humans in their slightly shorter and wider external auditory canal, smaller tympanic membrane, and lower malleus/incus lever ratio, but they remain primitive in the small size of their stapes footplate. Compared with chimpanzees, both early hominin taxa show a heightened sensitivity to frequencies between 1.5 and 3.5 kHz and an occupied band of maximum sensitivity that is shifted toward slightly higher frequencies. The results have implications for sensory ecology and communication, and suggest that the early hominin auditory pattern may have facilitated an increased emphasis on short-range vocal communication in open habitats.
Quam, Rolf; Martínez, Ignacio; Rosa, Manuel; Bonmatí, Alejandro; Lorenzo, Carlos; de Ruiter, Darryl J.; Moggi-Cecchi, Jacopo; Conde Valverde, Mercedes; Jarabo, Pilar; Menter, Colin G.; Thackeray, J. Francis; Arsuaga, Juan Luis
Studies of sensory capacities in past life forms have offered new insights into their adaptations and lifeways. Audition is particularly amenable to study in fossils because it is strongly related to physical properties that can be approached through their skeletal structures. We have studied the anatomy of the outer and middle ear in the early hominin taxa Australopithecus africanus and Paranthropus robustus and estimated their auditory capacities. Compared with chimpanzees, the early hominin taxa are derived toward modern humans in their slightly shorter and wider external auditory canal, smaller tympanic membrane, and lower malleus/incus lever ratio, but they remain primitive in the small size of their stapes footplate. Compared with chimpanzees, both early hominin taxa show a heightened sensitivity to frequencies between 1.5 and 3.5 kHz and an occupied band of maximum sensitivity that is shifted toward slightly higher frequencies. The results have implications for sensory ecology and communication, and suggest that the early hominin auditory pattern may have facilitated an increased emphasis on short-range vocal communication in open habitats. PMID:26601261
Full Text Available Optimal utilization of acoustic cues during auditory categorization is a vital skill, particularly when informative cues become occluded or degraded. Consequently, the acoustic environment requires flexible choosing and switching amongst available cues. The present study targets the brain functions underlying such changes in cue utilization. Participants performed a categorization task with immediate feedback on acoustic stimuli from two categories that varied in duration and spectral properties, while we simultaneously recorded Blood Oxygenation Level Dependent (BOLD responses in fMRI and electroencephalograms (EEGs. In the first half of the experiment, categories could be best discriminated by spectral properties. Halfway through the experiment, spectral degradation rendered the stimulus duration the more informative cue. Behaviorally, degradation decreased the likelihood of utilizing spectral cues. Spectrally degrading the acoustic signal led to increased alpha power compared to nondegraded stimuli. The EEG-informed fMRI analyses revealed that alpha power correlated with BOLD changes in inferior parietal cortex and right posterior superior temporal gyrus (including planum temporale. In both areas, spectral degradation led to a weaker coupling of BOLD response to behavioral utilization of the spectral cue. These data provide converging evidence from behavioral modeling, electrophysiology, and hemodynamics that (a increased alpha power mediates the inhibition of uninformative (here spectral stimulus features, and that (b the parietal attention network supports optimal cue utilization in auditory categorization. The results highlight the complex cortical processing of auditory categorization under realistic listening challenges.
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.
Singh, Komudi; Ju, Jennifer Y.; Walsh, Melissa B.; DiIorio, Michael A.; Hart, Anne C.
Objectives: Cross-species conservation of sleep-like behaviors predicts the presence of conserved molecular mechanisms underlying sleep. However, limited experimental evidence of conservation exists. Here, this prediction is tested directly. Measurements and Results: During lethargus, Caenorhabditis elegans spontaneously sleep in short bouts that are interspersed with bouts of spontaneous locomotion. We identified 26 genes required for Drosophila melanogaster sleep. Twenty orthologous C. elegans genes were selected based on similarity. Their effect on C. elegans sleep and arousal during the last larval lethargus was assessed. The 20 most similar genes altered both the quantity of sleep and arousal thresholds. In 18 cases, the direction of change was concordant with Drosophila studies published previously. Additionally, we delineated a conserved genetic pathway by which dopamine regulates sleep and arousal. In C. elegans neurons, G-alpha S, adenylyl cyclase, and protein kinase A act downstream of D1 dopamine receptors to regulate these behaviors. Finally, a quantitative analysis of genes examined herein revealed that C. elegans arousal thresholds were directly correlated with amount of sleep during lethargus. However, bout duration varies little and was not correlated with arousal thresholds. Conclusions: The comprehensive analysis presented here suggests that conserved genes and pathways are required for sleep in invertebrates and, likely, across the entire animal kingdom. The genetic pathway delineated in this study implicates G-alpha S and previously known genes downstream of dopamine signaling in sleep. Quantitative analysis of various components of quiescence suggests that interdependent or identical cellular and molecular mechanisms are likely to regulate both arousal and sleep entry. Citation: Singh K, Ju JY, Walsh MB, Dilorio MA, Hart AC. Deep conservation of genes required for both Drosophila melanogaster and Caenorhabditis elegans sleep includes a role for
Jepsen, Morten Løve; Dau, Torsten
Models of auditory signal processing and perception allow us to generate hypotheses that can be quantitatively tested, which in turn helps us to explain and understand the functioning of the auditory system. Here, the perceptual consequences of hearing impairment in individual listeners were...... investigated within the framework of the computational auditory signal processing and perception (CASP) model of Jepsen et al. [ J. Acoust. Soc. Am., in press]. Several parameters of the model were modified according to data from psychoacoustic measurements. Parameters associated with the cochlear stage were...... forward masking. The model may be useful for the evaluation of hearing-aid algorithms, where a reliable simulation of hearing impairment may reduce the need for time-consuming listening tests during development....
Full Text Available The extent to which auditory experience can shape general auditory perceptual abilities is still under constant debate. Some studies show that specific auditory expertise may have a general effect on auditory perceptual abilities, while others show a more limited influence, exhibited only in a relatively narrow range associated with the area of expertise. The current study addresses this issue by examining experience-dependent enhancement in perceptual abilities in the auditory domain. Three experiments were performed. In the first experiment, 12 pop and rock musicians and 15 non-musicians were tested in frequency discrimination (DLF, intensity discrimination, spectrum discrimination (DLS, and time discrimination (DLT. Results showed significant superiority of the musician group only for the DLF and DLT tasks, illuminating enhanced perceptual skills in the key features of pop music, in which miniscule changes in amplitude and spectrum are not critical to performance. The next two experiments attempted to differentiate between generalization and specificity in the influence of auditory experience, by comparing subgroups of specialists. First, seven guitar players and eight percussionists were tested in the DLF and DLT tasks that were found superior for musicians. Results showed superior abilities on the DLF task for guitar players, though no difference between the groups in DLT, demonstrating some dependency of auditory learning on the specific area of expertise. Subsequently, a third experiment was conducted, testing a possible influence of vowel density in native language on auditory perceptual abilities. Ten native speakers of German (a language characterized by a dense vowel system of 14 vowels, and 10 native speakers of Hebrew (characterized by a sparse vowel system of five vowels, were tested in a formant discrimination task. This is the linguistic equivalent of a DLS task. Results showed that German speakers had superior formant
Martin, Stephanie; Mikutta, Christian; Leonard, Matthew K; Hungate, Dylan; Koelsch, Stefan; Shamma, Shihab; Chang, Edward F; Millán, José Del R; Knight, Robert T; Pasley, Brian N
Despite many behavioral and neuroimaging investigations, it remains unclear how the human cortex represents spectrotemporal sound features during auditory imagery, and how this representation compares to auditory perception. To assess this, we recorded electrocorticographic signals from an epileptic patient with proficient music ability in 2 conditions. First, the participant played 2 piano pieces on an electronic piano with the sound volume of the digital keyboard on. Second, the participant replayed the same piano pieces, but without auditory feedback, and the participant was asked to imagine hearing the music in his mind. In both conditions, the sound output of the keyboard was recorded, thus allowing precise time-locking between the neural activity and the spectrotemporal content of the music imagery. This novel task design provided a unique opportunity to apply receptive field modeling techniques to quantitatively study neural encoding during auditory mental imagery. In both conditions, we built encoding models to predict high gamma neural activity (70-150 Hz) from the spectrogram representation of the recorded sound. We found robust spectrotemporal receptive fields during auditory imagery with substantial, but not complete overlap in frequency tuning and cortical location compared to receptive fields measured during auditory perception. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: firstname.lastname@example.org.
Full Text Available We have recently demonstrated that alternating left-right sound sources induce motion perception to static visual stimuli along the horizontal plane (SIVM: sound-induced visual motion perception, Hidaka et al., 2009. The aim of the current study was to elucidate whether auditory motion signals, rather than auditory positional signals, can directly contribute to the SIVM. We presented static visual flashes at retinal locations outside the fovea together with a lateral auditory motion provided by a virtual stereo noise source smoothly shifting in the horizontal plane. The flashes appeared to move in the situation where auditory positional information would have little influence on the perceived position of visual stimuli; the spatiotemporal position of the flashes was in the middle of the auditory motion trajectory. Furthermore, the auditory motion altered visual motion perception in a global motion display; in this display, different localized motion signals of multiple visual stimuli were combined to produce a coherent visual motion perception so that there was no clear one-to-one correspondence between the auditory stimuli and each visual stimulus. These findings suggest the existence of direct interactions between the auditory and visual modalities in motion processing and motion perception.
Bankoff, Richard J; Jerjos, Michael; Hohman, Baily; Lauterbur, M Elise; Kistler, Logan; Perry, George H
Several taxonomically distinct mammalian groups-certain microbats and cetaceans (e.g., dolphins)-share both morphological adaptations related to echolocation behavior and strong signatures of convergent evolution at the amino acid level across seven genes related to auditory processing. Aye-ayes (Daubentonia madagascariensis) are nocturnal lemurs with a specialized auditory processing system. Aye-ayes tap rapidly along the surfaces of trees, listening to reverberations to identify the mines of wood-boring insect larvae; this behavior has been hypothesized to functionally mimic echolocation. Here we investigated whether there are signals of convergence in auditory processing genes between aye-ayes and known mammalian echolocators. We developed a computational pipeline (Basic Exon Assembly Tool) that produces consensus sequences for regions of interest from shotgun genomic sequencing data for nonmodel organisms without requiring de novo genome assembly. We reconstructed complete coding region sequences for the seven convergent echolocating bat-dolphin genes for aye-ayes and another lemur. We compared sequences from these two lemurs in a phylogenetic framework with those of bat and dolphin echolocators and appropriate nonecholocating outgroups. Our analysis reaffirms the existence of amino acid convergence at these loci among echolocating bats and dolphins; some methods also detected signals of convergence between echolocating bats and both mice and elephants. However, we observed no significant signal of amino acid convergence between aye-ayes and echolocating bats and dolphins, suggesting that aye-aye tap-foraging auditory adaptations represent distinct evolutionary innovations. These results are also consistent with a developing consensus that convergent behavioral ecology does not reliably predict convergent molecular evolution. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.
Jones, Catherine R. G.; Happe, Francesca; Baird, Gillian; Simonoff, Emily; Marsden, Anita J. S.; Tregay, Jenifer; Phillips, Rebecca J.; Goswami, Usha; Thomson, Jennifer M.; Charman, Tony
It has been hypothesised that auditory processing may be enhanced in autism spectrum disorders (ASD). We tested auditory discrimination ability in 72 adolescents with ASD (39 childhood autism; 33 other ASD) and 57 IQ and age-matched controls, assessing their capacity for successful discrimination of the frequency, intensity and duration…
Basner, M.; Babisch, W.; Davis, A.; Brink, M.; Clark, C.; Janssen, S.A.; Stansfeld, S.
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
The Central Auditory Processing Kit[TM]. Book 1: Auditory Memory [and] Book 2: Auditory Discrimination, Auditory Closure, and Auditory Synthesis [and] Book 3: Auditory Figure-Ground, Auditory Cohesion, Auditory Binaural Integration, and Compensatory Strategies.
Mokhemar, Mary Ann
This kit for assessing central auditory processing disorders (CAPD), in children in grades 1 through 8 includes 3 books, 14 full-color cards with picture scenes, and a card depicting a phone key pad, all contained in a sturdy carrying case. The units in each of the three books correspond with auditory skill areas most commonly addressed in…
Furushima, Wakana; Kaga, Makiko; Nakamura, Masako; Gunji, Atsuko; Inagaki, Masumi
To investigate detailed auditory features in patients with auditory impairment as the first clinical symptoms of childhood adrenoleukodystrophy (CSALD). Three patients who had hearing difficulty as the first clinical signs and/or symptoms of ALD. Precise examination of the clinical characteristics of hearing and auditory function was performed, including assessments of pure tone audiometry, verbal sound discrimination, otoacoustic emission (OAE), and auditory brainstem response (ABR), as well as an environmental sound discrimination test, a sound lateralization test, and a dichotic listening test (DLT). The auditory pathway was evaluated by MRI in each patient. Poor response to calling was detected in all patients. Two patients were not aware of their hearing difficulty, and had been diagnosed with normal hearing by otolaryngologists at first. Pure-tone audiometry disclosed normal hearing in all patients. All patients showed a normal wave V ABR threshold. Three patients showed obvious difficulty in discriminating verbal sounds, environmental sounds, and sound lateralization and strong left-ear suppression in a dichotic listening test. However, once they discriminated verbal sounds, they correctly understood the meaning. Two patients showed elongation of the I-V and III-V interwave intervals in ABR, but one showed no abnormality. MRIs of these three patients revealed signal changes in auditory radiation including in other subcortical areas. The hearing features of these subjects were diagnosed as auditory agnosia and not aphasia. It should be emphasized that when patients are suspected to have hearing impairment but have no abnormalities in pure tone audiometry and/or ABR, this should not be diagnosed immediately as psychogenic response or pathomimesis, but auditory agnosia must also be considered. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
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.
Rizzo, Francesca; Coffman, James A; Arnone, Maria Ina
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. Copyright © 2016 Elsevier Inc. All rights reserved.
Wu, Calvin; Stefanescu, Roxana A; Martel, David T; Shore, Susan E
Conventionally, sensory systems are viewed as separate entities, each with its own physiological process serving a different purpose. However, many functions require integrative inputs from multiple sensory systems and sensory intersection and convergence occur throughout the central nervous system. The neural processes for hearing perception undergo significant modulation by the two other major sensory systems, vision and somatosensation. This synthesis occurs at every level of the ascending auditory pathway: the cochlear nucleus, inferior colliculus, medial geniculate body and the auditory cortex. In this review, we explore the process of multisensory integration from (1) anatomical (inputs and connections), (2) physiological (cellular responses), (3) functional and (4) pathological aspects. We focus on the convergence between auditory and somatosensory inputs in each ascending auditory station. This review highlights the intricacy of sensory processing and offers a multisensory perspective regarding the understanding of sensory disorders.
Yuasa-Kawada, Junichi; Kinoshita-Kawada, Mariko; Rao, Yi; Wu, Jane Y
Slit regulates migration of not only neurons, but also nonneuronal cells, such as leukocytes and cancer cells. Slit effect on cancer cell migration has not been well-characterized. In this study, we used several different assays to examine Slit effect on breast cancer cell migration in vitro. We show that ubiquitin-specific protease 33 (USP33)/VDU1, originally identified as a von Hippel-Lindau tumor suppressor (VHL) protein-interacting deubiquitinating enzyme, binds to the Robo1 receptor, and that USP33 is required for Slit responsiveness in breast cancer cells. Slit induces redistribution of Robo1 from intracellular compartments to the plasma membrane in a USP33-dependent manner. Slit impairs directional migration of breast cancer cells without affecting their migration speed. This inhibitory effect is Robo-mediated and USP33-dependent. These data uncover a previously unknown function of USP33 and reveal a new player in Slit-Robo signaling in cancer cell migration.
Sokol V Todi
Full Text Available BACKGROUND: Myosin VIIA (MyoVIIA is an unconventional myosin necessary for vertebrate audition -. Human auditory transduction occurs in sensory hair cells with a staircase-like arrangement of apical protrusions called stereocilia. In these hair cells, MyoVIIA maintains stereocilia organization . Severe mutations in the Drosophila MyoVIIA orthologue, crinkled (ck, are semi-lethal  and lead to deafness by disrupting antennal auditory organ (Johnston's Organ, JO organization . ck/MyoVIIA mutations result in apical detachment of auditory transduction units (scolopidia from the cuticle that transmits antennal vibrations as mechanical stimuli to JO. PRINCIPAL FINDINGS: Using flies expressing GFP-tagged NompA, a protein required for auditory organ organization in Drosophila, we examined the role of ck/MyoVIIA in JO development and maintenance through confocal microscopy and extracellular electrophysiology. Here we show that ck/MyoVIIA is necessary early in the developing antenna for initial apical attachment of the scolopidia to the articulating joint. ck/MyoVIIA is also necessary to maintain scolopidial attachment throughout adulthood. Moreover, in the adult JO, ck/MyoVIIA genetically interacts with the non-muscle myosin II (through its regulatory light chain protein and the myosin binding subunit of myosin II phosphatase. Such genetic interactions have not previously been observed in scolopidia. These factors are therefore candidates for modulating MyoVIIA activity in vertebrates. CONCLUSIONS: Our findings indicate that MyoVIIA plays evolutionarily conserved roles in auditory organ development and maintenance in invertebrates and vertebrates, enhancing our understanding of auditory organ development and function, as well as providing significant clues for future research.
Decorsière, Remi Julien Blaise; Søndergaard, Peter Lempel; MacDonald, Ewen
Envelope representations such as the auditory or traditional spectrogram can be defined by the set of envelopes from the outputs of a filterbank. Common envelope extraction methods discard information regarding the fast fluctuations, or phase, of the signal. Thus, it is difficult to invert, or re...... to the framework is proposed, which leads to a more accurate inversion of traditional spectrograms...
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…
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 ...
The transmitter and the receiver in a communication system have to be designed optimally with respect to one another to ensure reliable and efﬁcient communication. Following this principle, we derive an optimal ﬁlterbank for processing speech signal in the listener's auditory system (receiver), so that maximum information ...
Hudock, Daniel; Kalinowski, Joseph
Background: Overt stuttering is inhibited by approximately 80% when people who stutter read aloud as they hear an altered form of their speech feedback to them. However, levels of stuttering inhibition vary from 60% to 100% depending on speaking situation and signal presentation. For example, binaural presentations of delayed auditory feedback…
Kirste, Imke; Nicola, Zeina; Kronenberg, Golo; Walker, Tara L; Liu, Robert C; Kempermann, Gerd
We have previously hypothesized that the reason why physical activity increases precursor cell proliferation in adult neurogenesis is that movement serves as non-specific signal to evoke the alertness required to meet cognitive demands. Thereby a pool of immature neurons is generated that are potentially recruitable by subsequent cognitive stimuli. Along these lines, we here tested whether auditory stimuli might exert a similar non-specific effect on adult neurogenesis in mice. We used the standard noise level in the animal facility as baseline and compared this condition to white noise, pup calls, and silence. In addition, as patterned auditory stimulus without ethological relevance to mice we used piano music by Mozart (KV 448). All stimuli were transposed to the frequency range of C57BL/6 and hearing was objectified with acoustic evoked potentials. We found that except for white noise all stimuli, including silence, increased precursor cell proliferation (assessed 24 h after labeling with bromodeoxyuridine, BrdU). This could be explained by significant increases in BrdU-labeled Sox2-positive cells (type-1/2a). But after 7 days, only silence remained associated with increased numbers of BrdU-labeled cells. Compared to controls at this stage, exposure to silence had generated significantly increased numbers of BrdU/NeuN-labeled neurons. Our results indicate that the unnatural absence of auditory input as well as spectrotemporally rich albeit ethological irrelevant stimuli activate precursor cells-in the case of silence also leading to greater numbers of newborn immature neurons-whereas ambient and unstructured background auditory stimuli do not.
Peschke, C; Ziegler, W; Kappes, J; Baumgaertner, A
This fMRI study examined which structures of a proposed dorsal stream system are involved in the auditory-motor integration during fast overt repetition. We used a shadowing task which requires immediate repetition of an auditory-verbal input and is supposed to elicit unconscious imitation effects of phonologically irrelevant speech parameters. Subjects' responses were recorded in the scanner. To examine automated auditory-motor mapping of speech gestures of others onto one's own speech production system we contrasted the shadowing of pseudowords produced by multiple speakers (men, women, and children) with the shadowing of pseudowords produced by a single speaker. Furthermore, we asked whether behavioral variables predicted changes in functional activation during shadowing. Shadowing multiple speakers compared to a single speaker elicited increased bilateral activation predominantly in the superior temporal sulci. These regions may mediate acoustic-phonetic speaker normalization in preparation of a translation of perceptual into motor information. Additional activation in Broca's area and the thalamus may reflect motor effects of the adaptation to multiple speaker models. Item-wise correlational analyses of response latencies with BOLD signal changes indicated that longer latencies were associated with increased activation in the left parietal operculum, suggesting that this area plays a central role in the actual transfer of auditory-verbal information to speech motor representations. A multiple regression of behavioral with imaging data showed activation in a right inferior parietal area near the temporo-parietal boundary which correlated positively with the degree of speech rate imitation and negatively with response latency. This activation may be attributable to attentional and/or paralinguistic processes.
James Bigelow; Amy Poremba
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 o...
Simoens, Veerle L; Tervaniemi, Mari
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 such a complicated procedure. There were three parts in this study. First, professional musicians participated in an electroencephalographic (EEG) experiment to study the slow wave potentials during a time interval of short-term memory storage in a situation that requires cross-modal translation and short-term storage of visual material to be compared with delayed auditory material, as it is the case in music score reading. This delayed visual-to-auditory matching task was compared with delayed visual-visual and auditory-auditory matching tasks in terms of EEG topography and voltage amplitudes. Second, an additional behavioural experiment was performed to determine which type of distractor would be the most interfering with the score reading-like task. Third, the self-reported strategies of the participants were also analyzed. All three parts of this study point towards the same conclusion according to which during music score reading, the musician most likely first translates the visual score into an auditory cue, probably starting around 700 or 1300 ms, ready for storage and delayed comparison with the auditory feedback.
Veerle L Simoens
Full Text Available 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 such a complicated procedure. There were three parts in this study. First, professional musicians participated in an electroencephalographic (EEG experiment to study the slow wave potentials during a time interval of short-term memory storage in a situation that requires cross-modal translation and short-term storage of visual material to be compared with delayed auditory material, as it is the case in music score reading. This delayed visual-to-auditory matching task was compared with delayed visual-visual and auditory-auditory matching tasks in terms of EEG topography and voltage amplitudes. Second, an additional behavioural experiment was performed to determine which type of distractor would be the most interfering with the score reading-like task. Third, the self-reported strategies of the participants were also analyzed. All three parts of this study point towards the same conclusion according to which during music score reading, the musician most likely first translates the visual score into an auditory cue, probably starting around 700 or 1300 ms, ready for storage and delayed comparison with the auditory feedback.
Simoens, Veerle L.; Tervaniemi, Mari
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 such a complicated procedure. There were three parts in this study. First, professional musicians participated in an electroencephalographic (EEG) experiment to study the slow wave potentials during a time interval of short-term memory storage in a situation that requires cross-modal translation and short-term storage of visual material to be compared with delayed auditory material, as it is the case in music score reading. This delayed visual-to-auditory matching task was compared with delayed visual-visual and auditory-auditory matching tasks in terms of EEG topography and voltage amplitudes. Second, an additional behavioural experiment was performed to determine which type of distractor would be the most interfering with the score reading-like task. Third, the self-reported strategies of the participants were also analyzed. All three parts of this study point towards the same conclusion according to which during music score reading, the musician most likely first translates the visual score into an auditory cue, probably starting around 700 or 1300 ms, ready for storage and delayed comparison with the auditory feedback. PMID:23326487
J Gordon Millichap
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.
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
Brown, Jason M.; Sampaio, Julio L.; Craft, Julie M.; Shevchenko, Andrej; Evans, James E.; Witman, George B.
The BBSome is a complex of seven proteins, including BBS4, that is cycled through cilia by intraflagellar transport (IFT). Previous work has shown that the membrane-associated signaling protein phospholipase D (PLD) accumulates abnormally in cilia of Chlamydomonas reinhardtii bbs mutants. Here we show that PLD is a component of wild-type cilia but is enriched ∼150-fold in bbs4 cilia; this accumulation occurs progressively over time and results in altered ciliary lipid composition. When wild-type BBSomes were introduced into bbs cells, PLD was rapidly removed from the mutant cilia, indicating the presence of an efficient BBSome-dependent mechanism for exporting ciliary PLD. This export requires retrograde IFT. Importantly, entry of PLD into cilia is BBSome and IFT independent. Therefore, the BBSome is required only for the export phase of a process that continuously cycles PLD through cilia. Another protein, carbonic anhydrase 6, is initially imported normally into bbs4 cilia but lost with time, suggesting that its loss is a secondary effect of BBSome deficiency. PMID:23589493
Lucker, Jay R
Many audiologists believe that auditory processing testing must be carried out in a soundproof booth. This expectation is especially a problem in places such as elementary schools. Research comparing pure-tone thresholds obtained in sound booths compared to quiet test environments outside of these booths does not support that belief. Auditory processing testing is generally carried out at above threshold levels, and therefore may be even less likely to require a soundproof booth. The present study was carried out to compare test results in soundproof booths versus quiet rooms. The purpose of this study was to determine whether auditory processing tests can be administered in a quiet test room rather than in the soundproof test suite. The outcomes would identify that audiologists can provide auditory processing testing for children under various test conditions including quiet rooms at their school. A battery of auditory processing tests was administered at a test level equivalent to 50 dB HL through headphones. The same equipment was used for testing in both locations. Twenty participants identified with normal hearing were included in this study, ten having no auditory processing concerns and ten exhibiting auditory processing problems. All participants underwent a battery of tests, both inside the test booth and outside the booth in a quiet room. Order of testing (inside versus outside) was counterbalanced. Participants were first determined to have normal hearing thresholds for tones and speech. Auditory processing tests were recorded and presented from an HP EliteBook laptop computer with noise-canceling headphones attached to a y-cord that not only presented the test stimuli to the participants but also allowed monitor headphones to be worn by the evaluator. The same equipment was used inside as well as outside the booth. No differences were found for each auditory processing measure as a function of the test setting or the order in which testing was done
Hall, J; Hubbard, A; Neely, S; Tubis, A
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 . 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...
Wang, Xing-Yu; Zhou, Lian; Yang, Jun; Ji, Guang-Hai; He, Ya-Wen
Xanthomonas oryzae pv. oryzae, the bacterial blight pathogen of rice, produces diffusible signal factor (DSF) family quorum sensing signals to regulate virulence. The biosynthesis and perception of DSF family signals require components of the rpf (regulation of pathogenicity factors) cluster. In this study, we report that RpfB plays an essential role in DSF family signal turnover in X. oryzae pv. oryzae PXO99A. The production of DSF family signals was boosted by deletion of the rpfB gene and was abolished by its overexpression. The RpfC/RpfG-mediated DSF signaling system negatively regulates rpfB expression via the global transcription regulator Clp, whose activity is reversible in the presence of cyclic diguanylate monophosphate. These findings indicate that the DSF family signal turnover system in PXO99A is generally consistent with that in Xanthomonas campestris pv. campestris. Moreover, this study has revealed several specific roles of RpfB in PXO99A. First, the rpfB deletion mutant produced high levels of DSF family signals but reduced extracellular polysaccharide production, extracellular amylase activity, and attenuated pathogenicity. Second, the rpfB/rpfC double-deletion mutant was partially deficient in xanthomonadin production. Taken together, the RpfB-dependent DSF family signal turnover system is a conserved and naturally presenting signal turnover system in Xanthomonas spp., which plays unique roles in X. oryzae pv. oryzae adaptation and pathogenesis.
Lehmann, Alexandre; Skoe, Erika; Moreau, Patricia; Peretz, Isabelle; Kraus, Nina
Congenital amusia is a neurogenetic condition, characterized by a deficit in music perception and production, not explained by hearing loss, brain damage or lack of exposure to music. Despite inferior musical performance, amusics exhibit normal auditory cortical responses, with abnormal neural correlates suggested to lie beyond auditory cortices. Here we show, using auditory brainstem responses to complex sounds in humans, that fine-grained automatic processing of sounds is impoverished in amusia. Compared with matched non-musician controls, spectral amplitude was decreased in amusics for higher harmonic components of the auditory brainstem response. We also found a delayed response to the early transient aspects of the auditory stimulus in amusics. Neural measures of spectral amplitude and response timing correlated with participants' behavioral assessments of music processing. We demonstrate, for the first time, that amusia affects how complex acoustic signals are processed in the auditory brainstem. This neural signature of amusia mirrors what is observed in musicians, such that the aspects of the auditory brainstem responses that are enhanced in musicians are degraded in amusics. By showing that gradients of music abilities are reflected in the auditory brainstem, our findings have implications not only for current models of amusia but also for auditory functioning in general. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
Roberts Larry E
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.
Mizutani, Tatsuaki; Neugebauer, Nina; Putz, Eva M; Moritz, Nadine; Simma, Olivia; Zebedin-Brandl, Eva; Gotthardt, Dagmar; Warsch, Wolfgang; Eckelhart, Eva; Kantner, Hans-Peter; Kalinke, Ulrich; Lienenklaus, Stefan; Weiss, Siegfried; Strobl, Birgit; Müller, Mathias; Sexl, Veronika; Stoiber, Dagmar
Mice with an impaired Type I interferon (IFN) signaling (IFNAR1- and IFNβ-deficient mice) display an increased susceptibility toward v-ABL-induced B-cell leukemia/lymphoma. The enhanced leukemogenesis in the absence of an intact Type I IFN signaling is caused by alterations within the tumor environment. Deletion of Ifnar1 in tumor cells (as obtained in Ifnar1(f/f) CD19-Cre mice) failed to impact on disease latency or type. In line with this observation, the initial transformation and proliferative capacity of tumor cells were unaltered irrespective of whether the cells expressed IFNAR1 or not. v-ABL-induced leukemogenesis is mainly subjected to natural killer (NK) cell-mediated tumor surveillance. Thus, we concentrated on NK cell functions in IFNAR1 deficient animals. Ifnar1(-/-) NK cells displayed maturation defects as well as an impaired cytolytic activity. When we deleted Ifnar1 selectively in mature NK cells (by crossing Ncr1-iCre mice to Ifnar1(f/f) animals), maturation was not altered. However, NK cells derived from Ifnar1(f/f) Ncr1-iCre mice showed a significant cytolytic defect in vitro against the hematopoietic cell lines YAC-1 and RMA-S, but not against the melanoma cell line B16F10. Interestingly, this defect was not related to an in vivo phenotype as v-ABL-induced leukemogenesis was unaltered in Ifnar1(f/f )Ncr1-iCre compared with Ifnar1(f/f) control mice. Moreover, the ability of Ifnar1(f/f) Ncr1-iCre NK cells to kill B16F10 melanoma cells was unaltered, both in vitro and in vivo. Our data reveal that despite the necessity for Type I IFN in NK cell maturation the expression of IFNAR1 on mature murine NK cells is not required for efficient tumor surveillance.
Sala, Frederic G.; Ford, Henri R.; Bellusci, Saverio; Grikscheit, Tracy C.
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. PMID:23133671
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.
Van Stry, Melanie; Kazlauskas, Andrius; Schreiber, Stuart L.; Symes, Karen
Platelet-derived growth factor receptor (PDGFR) signaling is essential for normal embryonic development in many organisms, including frog, mouse, zebrafish, and sea urchin. The mode of action of PDGFR signaling during early development is poorly understood, however, mostly because inhibition of signaling through either the PDGFRα or PDGFRβ is embryonic lethal. In Xenopus embryos, disruption of PDGFRα signaling causes migrating anterior mesoderm cells to lose direction and undergo apoptosis th...
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.
Full Text Available While many studies have shown that visual information affects perception in the other modalities, little is known about how auditory and haptic information affect visual perception. In this study, we investigated how auditory, haptic, or auditory and haptic stimulation affects visual perception. We used a behavioral task based on the subjects observing the phenomenon of two identical visual objects moving toward each other, overlapping and then continuing their original motion. Subjects may perceive the objects as either streaming each other or bouncing and reversing their direction of motion. With only visual motion stimulus, subjects usually report the objects as streaming, whereas if a sound or flash is played when the objects touch each other, subjects report the objects as bouncing (Bounce-Inducing Effect. In this study, “auditory stimulation”, “haptic stimulation” or “haptic and auditory stimulation” were presented at various times relative to the visual overlap of objects. Our result shows the bouncing rate when haptic and auditory stimulation were presented were the highest. This result suggests that the Bounce-Inducing Effect is enhanced by simultaneous modality presentation to visual motion. In the future, a neuroscience approach (eg, TMS, fMRI may be required to elucidate the brain mechanism in this study.
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 present topics on signal processing which are important in a specific area of acoustics. These will be of interest to specialists in these areas because they will be presented from their technical perspective, rather than a generic engineering approach to signal processing. Non-specialists, or specialists...
Leiva, Alicia; Parmentier, Fabrice B R; Andrés, Pilar
Aging is typically considered to bring a reduction of the ability to resist distraction by task-irrelevant stimuli. Yet recent work suggests that this conclusion must be qualified and that the effect of aging is mitigated by whether irrelevant and target stimuli emanate from the same modalities or from distinct ones. Some studies suggest that aging is especially sensitive to distraction within-modality while others suggest it is greater across modalities. Here we report the first study to measure the effect of aging on deviance distraction in cross-modal (auditory-visual) and uni-modal (auditory-auditory) oddball tasks. Young and older adults were asked to judge the parity of target digits (auditory or visual in distinct blocks of trials), each preceded by a task-irrelevant sound (the same tone on most trials-the standard sound-or, on rare and unpredictable trials, a burst of white noise-the deviant sound). Deviant sounds yielded distraction (longer response times relative to standard sounds) in both tasks and age groups. However, an age-related increase in distraction was observed in the cross-modal task and not in the uni-modal task. We argue that aging might affect processes involved in the switching of attention across modalities and speculate that this may due to the slowing of this type of attentional shift or a reduction in cognitive control required to re-orient attention toward the target's modality.
Wolnicka-Glubisz, Agnieszka; Strickland, Faith M; Wielgus, Albert; Anver, Miriam; Merlino, Glenn; De Fabo, Edward C; Noonan, Frances P
Melanocortin 1 receptor (MC1R) signaling stimulates black eumelanin production through a cAMP-dependent pathway. MC1R polymorphisms can impair this process, resulting in a predominance of red phaeomelanin. The red hair, fair skin and UV sensitive phenotype is a well-described melanoma risk factor. MC1R polymorphisms also confer melanoma risk independent of pigment. We investigated the effect of Mc1r deficiency in a mouse model of UV-induced melanoma. C57BL/6-Mc1r+/+-HGF transgenic mice have a characteristic hyperpigmented black phenotype with extra-follicular dermal melanocytes located at the dermal/epidermal junction. UVB induces melanoma, independent of melanin pigmentation, but UVA-induced and spontaneous melanomas are dependent on black eumelanin. We crossed these mice with yellow C57BL/6-Mc1re/e animals which have a non-functional Mc1r and produce predominantly yellow phaeomelanin. Yellow C57BL/6-Mc1re/e-HGF mice produced no melanoma in response to UVR or spontaneously even though the HGF transgene and its receptor Met were expressed. Total melanin was less than in C57BL/6-Mc1r+/+-HGF mice, hyperpigmentation was not observed and there were few extra-follicular melanocytes. Thus, functional Mc1r was required for expression of the transgenic HGF phenotype. Heterozygous C57BL/6-Mc1re/+-HGF mice were black and hyperpigmented and, although extra-follicular melanocytes and skin melanin content were similar to C57BL/6-Mc1r+/+-HGF animals, they developed UV-induced and spontaneous melanomas with significantly less efficiency by all criteria. Thus, heterozygosity for Mc1r was sufficient to restore the transgenic HGF phenotype but insufficient to fully restore melanoma. We conclude that a previously unsuspected melanin-independent interaction between Mc1r and Met signaling pathways is required for HGF-dependent melanoma and postulate that this pathway is involved in human melanoma. 2014 UICC.
Wolnicka-Glubisz, Agnieszka; Strickland, Faith M.; Wielgus, Albert; Anver, Miriam; Merlino, Glenn; De Fabo, Edward C.; Noonan, Frances P.
Melanocortin 1 receptor (MC1R) signaling stimulates black eumelanin production through a cAMP dependent pathway. MC1R polymorphisms can impair this process, resulting in a predominance of red phaeomelanin. The red hair, fair skin and UV sensitive phenotype is a well-described melanoma risk factor. MC1R polymorphisms also confer melanoma risk independent of pigment. We investigated the effect of Mc1r deficiency in a mouse model of UV-induced melanoma. C57BL/6-Mc1r+/+-HGF transgenic mice have a characteristic hyperpigmented black phenotype with extra-follicular dermal melanocytes located at the dermal/epidermal junction. UVB induces melanoma, independent of melanin pigmentation, but UVA-induced and spontaneous melanomas are dependent on black eumelanin. We crossed these mice with yellow C57BL/6-Mc1re/e animals which have a non-functional Mc1r and produce predominantly yellow phaeomelanin. Yellow C57BL/6-Mc1re/e-HGF mice produced no melanoma in response to UVR or spontaneously even though the HGF transgene and its receptor Met were expressed. Total melanin was less than in C57BL/6-Mc1r+/+-HGF mice, hyperpigmentation was not observed and there were few extra-follicular melanocytes. Thus, functional Mc1r was required for expression of the transgenic HGF phenotype. Heterozygous C57BL/6-Mc1re/+-HGF mice were black and hyperpigmented and, although extra-follicular melanocytes and skin melanin content were similar to C57BL/6-Mc1r+/+-HGF animals, they developed UV-induced and spontaneous melanomas with significantly less efficiency by all criteria. Thus, heterozygosity for Mc1r was sufficient to restore the transgenic HGF phenotype but insufficient to fully restore melanoma. We conclude that a previously unsuspected melanin-independent interaction between Mc1r and Met signaling pathways is required for HGF-dependent melanoma and postulate that this pathway is involved in human melanoma. PMID:24975581
Full Text Available The present study focuses on auditory discrimination abilities in older adults aged 65-89 years. We applied the ‘Leipzig Inventory for Patient Psychoacoustic’ (LIPP, a psychoacoustic test battery specifically designed to identify deficits in central auditory processing. These tests quantify the just noticeable differences (JND for the three basic acoustic parameters (i.e. frequency, intensity, and signal duration. Three different test modes (monaural, dichotic signal/noise [s/n] and interaural were used, stimulus level was 35dB sensation level. The tests are designed as three-alternative forced-choice procedure with a maximum-likelihood procedure estimating p=0,5 correct response value. These procedures have proven to be highly efficient and provide a reliable outcome. The measurements yielded significant age-dependent deteriorations in the ability to discriminate single acoustic features pointing to progressive impairments in central auditory processing. The degree of deterioration was correlated to the different acoustic features and to the test modes. Most prominent, interaural frequency and signal duration discrimination at low test frequencies was elevated which indicates a deterioration of time- and phase-dependent processing at brain stem and cortical levels. LIPP proves to be an effective tool to identify basic pathophysiological mechanisms and the source of a specific impairment in auditory processing of the elderly.
A young man with chronic auditory hallucinations was treated according to the principle that increasing external auditory stimulation decreases the likelihood of auditory hallucinations. Listening to a radio through stereo headphones in conditions of low auditory stimulation eliminated the patient's hallucinations.
shifts in the auditory receptive field locations driven by afferent signals from vestibular system.
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.
Isnard, Vincent; Taffou, Marine; Viaud-Delmon, Isabelle; Suied, Clara
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.
Camilla A. Richmond
Full Text Available The intestinal epithelium serves as an essential barrier to the outside world and is maintained by functionally distinct populations of rapidly cycling intestinal stem cells (CBC ISCs and slowly cycling, reserve ISCs (r-ISCs. Because disruptions in the epithelial barrier can result from pathological activation of the immune system, we sought to investigate the impact of inflammation on ISC behavior during the regenerative response. In a murine model of αCD3 antibody-induced small-intestinal inflammation, r-ISCs proved highly resistant to injury, while CBC ISCs underwent apoptosis. Moreover, r-ISCs were induced to proliferate and functionally contribute to intestinal regeneration. Further analysis revealed that the inflammatory cytokines interferon gamma and tumor necrosis factor alpha led to r-ISC activation in enteroid culture, which could be blocked by the JAK/STAT inhibitor, tofacitinib. These results highlight an important role for r-ISCs in response to acute intestinal inflammation and show that JAK/STAT-1 signaling is required for the r-ISC regenerative response.
Kim, Jong-Hyun; Sohn, Hae-Jin; Lee, Sang-Hee; Kwon, Daeho; Shin, Ho-Joon
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.
Hill, Matthew N.; Titterness, Andrea K.; Morrish, Anna C.; Carrier, Erica J.; Lee, Tiffany T.-Y.; Gil-Mohapel, Joana; Gorzalka, Boris B.; Hillard, Cecilia J.; Christie, Brian R.
Voluntary exercise and endogenous cannabinoid activity have independently been shown to regulate hippocampal plasticity. The aim of the current study was to determine whether the endocannabinoid system is regulated by voluntary exercise and if these changes contribute to exercise-induced enhancement of cell proliferation. In Experiment 1, eight days of free access to a running wheel increased the agonist binding site density of the cannabinoid CB1 receptor; CB1 receptor-mediated GTPγS binding; and the tissue content of the endocannabinoid anandamide in the hippocampus but not in the prefrontal cortex. In Experiment 2, the CB1 receptor antagonist AM251 (1 mg/kg) was administered daily to animals given free access to a running wheel for 8 days, after which cell proliferation in the hippocampus was examined through immunohistochemical analysis of the cell cycle protein Ki-67. Voluntary exercise increased proliferation of progenitor cells, as evidenced by the increase in the number of Ki-67 positive cells in the granule cell layer of the dentate gyrus in the hippocampus. However, this effect was abrogated by concurrent treatment with AM251, indicating that the increase in endocannabinoid signaling in the hippocampus is required for the exercise-induced increase in cell proliferation. These data demonstrate that the endocannabinoid system in the hippocampus is sensitive to environmental change and suggest that it is a mediator of experience-induced plasticity. PMID:19489006
Santisree, Parankusam; Nongmaithem, Sapana; Vasuki, Himabindu; Sreelakshmi, Yellamaraju; Ivanchenko, Maria G.; Sharma, Rameshwar
During seed germination, emerging roots display positive gravitropism and penetrate into the soil for nutrition and anchorage. Tomato (Solanum lycopersicum) seeds germinated in the presence of 1-methylcyclopropene (1-MCP), an inhibitor of ethylene action, failed to insert roots into Soilrite and grew in the air, forming loops. Time-lapse video imaging showed that 1-MCP-grown root tips retained positive gravitropism and made contact with the surface of Soilrite but failed to penetrate into the Soilrite. Time-course studies revealed that the effect of 1-MCP was most prominent when seed imbibition and germination were carried out in the continual presence of 1-MCP. Conversely, 1-MCP was ineffective when applied postgermination after penetration of roots in the Soilrite. Furthermore, treatment with 1-MCP caused a reduction in DR5::β-glucuronidase auxin-reporter activity and modified the expression of SlIAA3 and SlIAA9 transcripts, indicating interference with auxin signaling. The reduced ethylene perception mutant, Never-ripe, displayed decreased ability for root penetration, and the enhanced polar auxin transport mutant, polycotyledon, showed a nearly normal root penetration in the presence of 1-MCP, which could be reversed by application of auxin transport inhibitors. Our results indicate that during tomato seed germination, a coaction between ethylene and auxin is required for root penetration into the soil. PMID:21571667
Lv, Xiang-guang; Shi, Yong-feng; Xu, Xia; Wei, Yan-lin; Wang, Hui-mei; Zhang, Xiao-bo; Wu, Jian-li
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.
Jackson, Thomas E; Sandramouli, Soupramanien
Synesthesia is an unusual condition in which stimulation of one sensory modality causes an experience in another sensory modality or when a sensation in one sensory modality causes another sensation within the same modality. We describe a previously unreported association of auditory-olfactory synesthesia coexisting with auditory-visual synesthesia. Given that many types of synesthesias involve vision, it is important that the clinician provide these patients with the necessary information and support that is available.
Groen, Wouter B.; van Orsouw, Linda; ter Huurne, Niels; Swinkels, Sophie; van der Gaag, Rutger-Jan; Buitelaar, Jan K.; Zwiers, Marcel P.
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 high-functioning-autism and 23 matched controls…
Nívea Franklin Chaves Martins; Hipólito Virgílio Magalhães Jr
The aim of this case report was to promote a reflection about the importance of speech-therapy for stimulation a person with learning disability associated to language and auditory processing disorders. Data analysis considered the auditory abilities deficits identified in the first auditory processing test, held on April 30,2002 compared with the new auditory processing test done on May 13,2003,after one year of therapy directed to acoustic stimulation of auditory abilities disorders,in acco...
Parks, Anthony J.
How do listener head rotations affect auditory perception of elevation? This investi-. gation addresses this in the hopes that perceptual judgments of elevated auditory. percepts may be more thoroughly understood in terms of dynamic listening cues. engendered by listener head rotations and that this phenomenon can be psychophys-. ically and computationally modeled. Two listening tests were conducted and a. psychophysical model was constructed to this end. The frst listening test prompted. listeners to detect an elevated auditory event produced by a virtual noise source. orbiting the median plane via 24-channel ambisonic spatialization. Head rotations. were tracked using computer vision algorithms facilitated by camera tracking. The. data were used to construct a dichotomous criteria model using factorial binary. logistic regression model. The second auditory test investigated the validity of the. historically supported frequency dependence of auditory elevation perception using. narrow-band noise for continuous and brief stimuli with fxed and free-head rotation. conditions. The data were used to construct a multinomial logistic regression model. to predict categorical judgments of above, below, and behind. Finally, in light. of the psychophysical data found from the above studies, a functional model of. elevation perception for point sources along the cone of confusion was constructed. using physiologically-inspired signal processing methods along with top-down pro-. cessing utilizing principles of memory and orientation. The model is evaluated using. white noise bursts for 42 subjects' head-related transfer functions. The investigation. concludes with study limitations, possible implications, and speculation on future. research trajectories.
Full Text Available Neurotrophic factor and cAMP-dependent signaling promote the survival and neurite outgrowth of retinal ganglion cells (RGCs after injury. However, the mechanisms conferring neuroprotection and neuroregeneration downstream to these signals are unclear. We now reveal that the scaffold protein muscle A-kinase anchoring protein-α (mAKAPα is required for the survival and axon growth of cultured primary RGCs. Although genetic deletion of mAKAPα early in prenatal RGC development did not affect RGC survival into adulthood, nor promoted the death of RGCs in the uninjured adult retina, loss of mAKAPα in the adult increased RGC death after optic nerve crush. Importantly, mAKAPα was required for the neuroprotective effects of brain-derived neurotrophic factor and cyclic adenosine-monophosphate (cAMP after injury. These results identify mAKAPα as a scaffold for signaling in the stressed neuron that is required for RGC neuroprotection after optic nerve injury.
Conrad, Verena; Kleiner, Mario; Bartels, Andreas; Hartcher O'Brien, Jessica; Bülthoff, Heinrich H; Noppeney, Uta
Rapid integration of biologically relevant information is crucial for the survival of an organism. Most prominently, humans should be biased to attend and respond to looming stimuli that signal approaching danger (e.g. predator) and hence require rapid action. This psychophysics study used binocular rivalry to investigate the perceptual advantage of looming (relative to receding) visual signals (i.e. looming bias) and how this bias can be influenced by concurrent auditory looming/receding stimuli and the statistical structure of the auditory and visual signals. Subjects were dichoptically presented with looming/receding visual stimuli that were paired with looming or receding sounds. The visual signals conformed to two different statistical structures: (1) a 'simple' random-dot kinematogram showing a starfield and (2) a "naturalistic" visual Shepard stimulus. Likewise, the looming/receding sound was (1) a simple amplitude- and frequency-modulated (AM-FM) tone or (2) a complex Shepard tone. Our results show that the perceptual looming bias (i.e. the increase in dominance times for looming versus receding percepts) is amplified by looming sounds, yet reduced and even converted into a receding bias by receding sounds. Moreover, the influence of looming/receding sounds on the visual looming bias depends on the statistical structure of both the visual and auditory signals. It is enhanced when audiovisual signals are Shepard stimuli. In conclusion, visual perception prioritizes processing of biologically significant looming stimuli especially when paired with looming auditory signals. Critically, these audiovisual interactions are amplified for statistically complex signals that are more naturalistic and known to engage neural processing at multiple levels of the cortical hierarchy.
Jason D Wittenbach
Full Text Available Consecutive repetition of actions is common in behavioral sequences. Although integration of sensory feedback with internal motor programs is important for sequence generation, if and how feedback contributes to repetitive actions is poorly understood. Here we study how auditory feedback contributes to generating repetitive syllable sequences in songbirds. We propose that auditory signals provide positive feedback to ongoing motor commands, but this influence decays as feedback weakens from response adaptation during syllable repetitions. Computational models show that this mechanism explains repeat distributions observed in Bengalese finch song. We experimentally confirmed two predictions of this mechanism in Bengalese finches: removal of auditory feedback by deafening reduces syllable repetitions; and neural responses to auditory playback of repeated syllable sequences gradually adapt in sensory-motor nucleus HVC. Together, our results implicate a positive auditory-feedback loop with adaptation in generating repetitive vocalizations, and suggest sensory adaptation is important for feedback control of motor sequences.
Riskind, John H; Kleiman, Evan M; Seifritz, Erich; Neuhoff, John
Previous studies show that individuals with an anticipatory auditory looming bias over-estimate the closeness of a sound source that approaches them. Our present study bridges cognitive clinical and perception research, and provides evidence that anxiety symptoms and a particular putative cognitive style that creates vulnerability for anxiety (looming cognitive style, or LCS) are related to how people perceive this ecologically fundamental auditory warning signal. The effects of anxiety symptoms on the anticipatory auditory looming effect synergistically depend on the dimension of perceived personal danger assessed by the LCS (physical or social threat). Depression symptoms, in contrast to anxiety symptoms, predict a diminution of the auditory looming bias. Findings broaden our understanding of the links between cognitive-affective states and auditory perception processes and lend further support to past studies providing evidence that the looming cognitive style is related to bias in threat processing. Copyright © 2013 Elsevier Ltd. All rights reserved.
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.
Zacharias, Amanda L; Gage, Philip J
Pitx2 is a paired-like homeodomain gene that acts as a key regulator of eye development. Despite its significance, upstream regulation of Pitx2 expression during eye development remains incompletely understood. We use neural crest-specific ablation of Ctnnb1 to demonstrate that canonical Wnt signaling is not required for initial activation of Pitx2 in neural crest. However, canonical Wnt signaling is subsequently required to maintain Pitx2 expression in the neural crest. Eye development in Ctnnb1-null mice appears grossly normal early but significant phenotypes emerge following loss of Pitx2 expression. LEF-1 and β-catenin bind Pitx2 promoter sequences in ocular neural crest, indicating a likely direct effect of canonical Wnt signaling on Pitx2 expression. Combining our data with previous reports, we propose a model wherein a sequential code of retinoic acid followed by canonical Wnt signaling are required for activation and maintenance of Pitx2 expression, respectively. Other key transcription factors in the neural crest, including Foxc1, do not require intact canonical Wnt signaling. Copyright © 2010 Wiley-Liss, Inc.
Banai, Karen; Ahissar, Merav
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 memory skills are less
Banai, Karen; Ahissar, Merav
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. 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. 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 memory skills are less likely to study music and if so, why this is the case.
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
Contesto, Céline; Milesi, Sandrine; Mantelin, Sophie; Zancarini, Anouk; Desbrosses, Guilhem; Varoquaux, Fabrice; Bellini, Catherine; Kowalczyk, Mariusz; Touraine, Bruno
Plant root development is highly responsive both to changes in nitrate availability and beneficial microorganisms in the rhizosphere. We previously showed that Phyllobacterium brassicacearum STM196, a plant growth-promoting rhizobacteria strain isolated from rapeseed roots, alleviates the inhibition exerted by high nitrate supply on lateral root growth. Since soil-borne bacteria can produce IAA and since this plant hormone may be implicated in the high nitrate-dependent control of lateral root development, we investigated its role in the root development response of Arabidopsis thaliana to STM196. Inoculation with STM196 resulted in a 50% increase of lateral root growth in Arabidopsis wild-type seedlings. This effect was completely abolished in aux1 and axr1 mutants, altered in IAA transport and signaling, respectively, indicating that these pathways are required. The STM196 strain, however, appeared to be a very low IAA producer when compared with the high-IAA-producing Azospirillum brasilense sp245 strain and its low-IAA-producing ipdc mutant. Consistent with the hypothesis that STM196 does not release significant amounts of IAA to the host roots, inoculation with this strain failed to increase root IAA content. Inoculation with STM196 led to increased expression levels of several IAA biosynthesis genes in shoots, increased Trp concentration in shoots, and increased auxin-dependent GUS staining in the root apices of DR5::GUS transgenic plants. All together, our results suggest that STM196 inoculation triggers changes in IAA distribution and homeostasis independently from IAA release by the bacteria.
Rivollier, Aymeric Marie Christian; Pool, Lieneke; Frising, Ulrika
of intestinal inflammation in the T cell transfer colitis model. RA signalling-deficient CD4+ T cells are less potent at inducing intestinal inflammation compared to their RA signalling-proficient counterparts and exhibit a differentiation skewing towards more IL-17+ and foxp3+ cells, while their capacity...
Grossi, Alberto; Karlsson, Anders H; Lawson, Moira Ann
tissues. Stimulation due to stretch- or load-induced signaling is now beginning to be understood as a factor which affects various signal transduction pathways, gene sequences and protein synthesis. Evidence of the involvement of mitogen-activated protein kinase (MAPK) cascade activation in myoblast...
Jørgensen, Niklas R; Henriksen, Zanne; Sørensen, Ole
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...
Hamdoun, Safae; Gao, Min; Gill, Manroop; Kwon, Ashley; Norelli, John L; Lu, Hua
Erwinia amylovora is the causal agent of the fire blight disease in some plants of the Rosaceae family. The non-host plant Arabidopsis serves as a powerful system for the dissection of mechanisms of resistance to E. amylovora. Although not yet known to mount gene-for-gene resistance to E. amylovora, we found that Arabidopsis activated strong defence signalling mediated by salicylic acid (SA), with kinetics and amplitude similar to that induced by the recognition of the bacterial effector avrRpm1 by the resistance protein RPM1. Genetic analysis further revealed that SA signalling, but not signalling mediated by ethylene (ET) and jasmonic acid (JA), is required for E. amylovora resistance. Erwinia amylovora induces massive callose deposition on infected leaves, which is independent of SA, ET and JA signalling and is necessary for E. amylovora resistance in Arabidopsis. We also observed tumour-like growths on E. amylovora-infected Arabidopsis leaves, which contain enlarged mesophyll cells with increased DNA content and are probably a result of endoreplication. The formation of such growths is largely independent of SA signalling and some E. amylovora effectors. Together, our data reveal signalling requirements for E. amylovora-induced disease resistance, callose deposition and cell fate change in the non-host plant Arabidopsis. Knowledge from this study could facilitate a better understanding of the mechanisms of host defence against E. amylovora and eventually improve host resistance to the pathogen. © 2017 BSPP AND JOHN WILEY & SONS LTD.
Caroline Nunes Rocha-Muniz
Full Text Available INTRODUCTION: Mismatch negativity, an electrophysiological measure, evaluates the brain's capacity to discriminate sounds, regardless of attentional and behavioral capacity. Thus, this auditory event-related potential is promising in the study of the neurophysiological basis underlying auditory processing.OBJECTIVE: To investigate complex acoustic signals (speech encoded in the auditory nervous system of children with specific language impairment and compare with children with auditory processing disorders and typical development through the mismatch negativity paradigm.METHODS: It was a prospective study. 75 children (6-12 years participated in this study: 25 children with specific language impairment, 25 with auditory processing disorders, and 25 with typical development. Mismatch negativity was obtained by subtracting from the waves obtained by the stimuli /ga/ (frequent and /da/ (rare. Measures of mismatch negativity latency and two amplitude measures were analyzed.RESULTS: It was possible to verify an absence of mismatch negativity in 16% children with specific language impairment and 24% children with auditory processing disorders. In the comparative analysis, auditory processing disorders and specific language impairment showed higher latency values and lower amplitude values compared to typical development.CONCLUSION: These data demonstrate changes in the automatic discrimination of crucial acoustic components of speech sounds in children with specific language impairment and auditory processing disorders. It could indicate problems in physiological processes responsible for ensuring the discrimination of acoustic contrasts in pre-attentional and pre-conscious levels, contributing to poor perception.
Ross, Jessica Marie; Balasubramaniam, Ramesh
The contributions of somatosensory, vestibular, and visual feedback to balance control are well documented, but the influence of auditory information, especially acoustic noise, on balance is less clear. Because somatosensory noise has been shown to reduce postural sway, we hypothesized that noise from the auditory modality might have a similar effect. Given that the nervous system uses noise to optimize signal transfer, adding mechanical or auditory noise should lead to increased feedback about sensory frames of reference used in balance control. In the present experiment, postural sway was analyzed in healthy young adults where they were presented with continuous white noise, in the presence and absence of visual information. Our results show reduced postural sway variability (as indexed by the body's center of pressure) in the presence of auditory noise, even when visual information was not present. Nonlinear time series analysis revealed that auditory noise has an additive effect, independent of vision, on postural stability. Further analysis revealed that auditory noise reduced postural sway variability in both low- and high-frequency regimes (> or noise. Our results support the idea that auditory white noise reduces postural sway, suggesting that auditory noise might be used for therapeutic and rehabilitation purposes in older individuals and those with balance disorders.
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)
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.)
Rocha-Muniz, Caroline Nunes; Befi-Lopes, Débora Maria; Schochat, Eliane
Mismatch negativity, an electrophysiological measure, evaluates the brain's capacity to discriminate sounds, regardless of attentional and behavioral capacity. Thus, this auditory event-related potential is promising in the study of the neurophysiological basis underlying auditory processing. To investigate complex acoustic signals (speech) encoded in the auditory nervous system of children with specific language impairment and compare with children with auditory processing disorders and typical development through the mismatch negativity paradigm. It was a prospective study. 75 children (6-12 years) participated in this study: 25 children with specific language impairment, 25 with auditory processing disorders, and 25 with typical development. Mismatch negativity was obtained by subtracting from the waves obtained by the stimuli /ga/ (frequent) and /da/ (rare). Measures of mismatch negativity latency and two amplitude measures were analyzed. It was possible to verify an absence of mismatch negativity in 16% children with specific language impairment and 24% children with auditory processing disorders. In the comparative analysis, auditory processing disorders and specific language impairment showed higher latency values and lower amplitude values compared to typical development. These data demonstrate changes in the automatic discrimination of crucial acoustic components of speech sounds in children with specific language impairment and auditory processing disorders. It could indicate problems in physiological processes responsible for ensuring the discrimination of acoustic contrasts in pre-attentional and pre-conscious levels, contributing to poor perception. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.
Sapir, S; McClean, M D; Luschei, E S
The sensitivity of audio-laryngeal reflex pathways to sinusoidal changes in the fundamental frequency of complex auditory tones (AF0) was assessed indirectly in three young adult human subjects. The subjects sustained phonation at constant voice fundamental frequency (VF0) and voice intensity while listening to a sawtooth tone whose AF0 varied over time in a sinusoidal fashion (rates = 5-13 Hz). The subjects phonated at a low voice intensity so that the intensity of the auditory tone (80-85 dB SL) completely masked their voice. Using computer signal averaging and Fourier analysis techniques it was found that the sinusoidally modulated AF0 induced similar modulations in the VF0 signal. The VF0 modulations were extremely small in amplitude and showed large phase shifts relative to the auditory input. These findings are discussed in relation to the role of auditory feedback in phonatory control.
Full Text Available Research on auditory verbal hallucinations (AVHs indicates that AVH schizophrenia patients show greater abnormalities on tasks requiring recognition of affective prosody (AP than non-AVH patients. Detecting AP requires accurate perception of manipulations in pitch, amplitude and duration. Schizophrenia patients with AVHs also experience difficulty detecting these acoustic manipulations; with a number of theorists speculating that difficulties in pitch, amplitude and duration discrimination underlie AP abnormalities. This study examined whether both AP and these aspects of auditory processing are also impaired in first degree relatives of persons with AVHs. It also examined whether pitch, amplitude and duration discrimination were related to AP, and to hallucination proneness. Unaffected relatives of AVH schizophrenia patients (N=19 and matched healthy controls (N=33 were compared using tone discrimination tasks, an AP task, and clinical measures. Relatives were slower at identifying emotions on the AP task (p =.002, with secondary analysis showing this was especially so for happy (p = .014 and neutral (p =.001 sentences. There was a significant interaction effect for pitch between tone deviation level and group (p = .019, and relatives performed worse than controls on amplitude discrimination and duration discrimination. AP performance for happy and neutral sentences was significantly correlated with amplitude perception. Lastly, AVH proneness in the entire sample was significantly correlated with pitch discrimination (r = .44 and pitch perception was shown to predict AVH proneness in the sample (p = .005. These results suggest basic impairments in auditory processing are present in relatives of AVH patients; they potentially underlie processing speed in AP tasks, and predict AVH proneness. This indicates auditory processing deficits may be a core feature of AVHs in schizophrenia, and are worthy of further study as a potential endophenotype for
Zhou, Sijie; Allison, Brendan Z; Kübler, Andrea; Cichocki, Andrzej; Wang, Xingyu; Jin, Jing
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.
Full Text Available 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.
Maier, R; Rebentisch, E
It is well known, amplitudes and latencies of auditory brain stem potentials are almost independent of viligance state. Contrary to that, simple cognitive requirements effect amplitude changes (enhancement of variance, amplitude reduction) in a part 2/3) of the subjects.
Holtkotte, Xu; Ponnu, Jathish; Ahmad, Margaret; Hoecker, Ute
Plants constantly adjust their growth, development and metabolism to the ambient light environment. Blue light is sensed by the Arabidopsis photoreceptors CRY1 and CRY2 which subsequently initiate light signal transduction by repressing the COP1/SPA E3 ubiquitin ligase. While the interaction between cryptochromes and SPA is blue light-dependent, it was proposed that CRY1 interacts with COP1 constitutively, i.e. also in darkness. Here, our in vivo co-immunoprecipitation experiments suggest that CRY1 and CRY2 form a complex with COP1 only after seedlings were exposed to blue light. No association between COP1 and CRY1 or CRY2 was observed in dark-grown seedlings. Thus, our results suggest that cryptochromes bind the COP1/SPA complex after photoactivation by blue light. In a spa quadruple mutant that is devoid of all four SPA proteins, CRY1 and COP1 did not interact in vivo, neither in dark-grown nor in blue light-grown seedlings. Hence, SPA proteins are required for the high-affinity interaction between CRY1 and COP1 in blue light. Yeast three-hybrid experiments also show that SPA1 enhances the CRY1-COP1 interaction. The coiled-coil domain of SPA1 which is responsible for COP1-binding was necessary to mediate a CRY1-SPA1 interaction in vivo, implying that-in turn-COP1 may be necessary for a CRY1-SPA1 complex formation. Hence, SPA1 and COP1 may act cooperatively in recognizing and binding photoactivated CRY1. In contrast, the blue light-induced association between CRY2 and COP1 was not dependent on SPA proteins in vivo. Similarly, ΔCC-SPA1 interacted with CRY2, though with a much lower affinity than wild-type SPA1. In total, our results demonstrate that CRY1 and CRY2 strongly differ in their blue light-induced interaction with the COP1/SPA complex.
Full Text Available Abstract Background Wnt/Wingless (Wg signals are transduced by seven-transmembrane Frizzleds (Fzs and the single-transmembrane LDL-receptor-related proteins 5 or 6 (LRP5/6 or Arrow. The aminotermini of LRP and Fz were reported to associate only in the presence of Wnt, implying that Wnt ligands form a trimeric complex with two different receptors. However, it was recently reported that LRPs activate the Wnt/β-catenin pathway by binding to Axin in a Dishevelled – independent manner, while Fzs transduce Wnt signals through Dishevelled to stabilize β-catenin. Thus, it is possible that Wnt proteins form separate complexes with Fzs and LRPs, transducing Wnt signals separately, but converging downstream in the Wnt/β-catenin pathway. The question then arises whether both receptors are absolutely required to transduce Wnt signals. Results We have established a sensitive luciferase reporter assay in Drosophila S2 cells to determine the level of Wg – stimulated signaling. We demonstrate here that Wg can synergize with DFz2 and function cooperatively with LRP to activate the β-catenin/Armadillo signaling pathway. Double-strand RNA interference that disrupts the synthesis of either receptor type dramatically impairs Wg signaling activity. Importantly, the pronounced synergistic effect of adding Wg and DFz2 is dependent on Arrow and Dishevelled. The synergy requires the cysteine-rich extracellular domain of DFz2, but not its carboxyterminus. Finally, mammalian LRP6 and its activated forms, which lack most of the extracellular domain of the protein, can activate the Wg signaling pathway and cooperate with Wg and DFz2 in S2 cells. We also show that the aminoterminus of LRP/Arr is required for the synergy between Wg and DFz2. Conclusion Our study indicates that Wg signal transduction in S2 cells depends on the function of both LRPs and DFz2, and the results are consistent with the proposal that Wnt/Wg signals through the aminoterminal domains of its dual
Gil-Carvajal, Juan C.; Cubick, Jens; Santurette, Sébastien; Dau, Torsten
In day-to-day life, humans usually perceive the location of sound sources as outside their heads. This externalized auditory spatial perception can be reproduced through headphones by recreating the sound pressure generated by the source at the listener’s eardrums. This requires the acoustical features of the recording environment and listener’s anatomy to be recorded at the listener’s ear canals. Although the resulting auditory images can be indistinguishable from real-world sources, their externalization may be less robust when the playback and recording environments differ. Here we tested whether a mismatch between playback and recording room reduces perceived distance, azimuthal direction, and compactness of the auditory image, and whether this is mostly due to incongruent auditory cues or to expectations generated from the visual impression of the room. Perceived distance ratings decreased significantly when collected in a more reverberant environment than the recording room, whereas azimuthal direction and compactness remained room independent. Moreover, modifying visual room-related cues had no effect on these three attributes, while incongruent auditory room-related cues between the recording and playback room did affect distance perception. Consequently, the external perception of virtual sounds depends on the degree of congruency between the acoustical features of the environment and the stimuli.
Knopp, M; Leese, R J; Martin-Lamb, D; Rajabally, Y A
The involvement of optic and auditory pathways has rarely been studied in demyelinating polyneuropathies. We here aimed to study this further in a cohort of patients with acquired and gentic demyelinating neuropathy. We studied eight patients with hereditary neuropathy with liability to pressure palsies (HNPP), six with Charcot-Marie-Tooth disease type 1A (CMT1A), ten with chronic inflammatory demyelinating polyneuropathy (CIDP) and seven with antimyelin-associated glycoprotein (MAG) neuropathy using visual evoked potentials and brainstem auditory evoked potentials. Optic pathway dysfunction was detected in 6/7 anti-MAG neuropathy patients, about half of those with CIDP and HNPP, but only in 1/6 patients with CMT1A. Peripheral auditory nerve dysfunction appeared common in all groups except HNPP. Brainstem involvement was exceptional in all groups. We conclude optic nerve involvement may be frequent in all demyelinating polyneuropathies, particularly anti-MAG neuropathy, except in CMT1A. Peripheral auditory nerves may be spared in HNPP possibly due to absence of local compression. Evidence for central brainstem pathology appeared infrequent in all four studied neuropathies. This study suggests that acquired and genetic demyelinating polyneuropathies may be associated with optic and auditory nerve involvement, which may contribute to neurological disability, and require greater awareness. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Higgins, Nathan C.; Storace, Douglas A.; Escabí, Monty A.
Accurate orientation to sound under challenging conditions requires auditory cortex, but it is unclear how spatial attributes of the auditory scene are represented at this level. Current organization schemes follow a functional division whereby dorsal and ventral auditory cortices specialize to encode spatial and object features of sound source, respectively. However, few studies have examined spatial cue sensitivities in ventral cortices to support or reject such schemes. Here Fourier optical imaging was used to quantify best frequency responses and corresponding gradient organization in primary (A1), anterior, posterior, ventral (VAF), and suprarhinal (SRAF) auditory fields of the rat. Spike rate sensitivities to binaural interaural level difference (ILD) and average binaural level cues were probed in A1 and two ventral cortices, VAF and SRAF. Continuous distributions of best ILDs and ILD tuning metrics were observed in all cortices, suggesting this horizontal position cue is well covered. VAF and caudal SRAF in the right cerebral hemisphere responded maximally to midline horizontal position cues, whereas A1 and rostral SRAF responded maximally to ILD cues favoring more eccentric positions in the contralateral sound hemifield. SRAF had the highest incidence of binaural facilitation for ILD cues corresponding to midline positions, supporting current theories that auditory cortices have specialized and hierarchical functional organization. PMID:20980610
Caroline Nunes Rocha-Muniz
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.
Yu-Wai-Man, Patrick; Elliott, Clive; Griffiths, Philip G; Johnson, Ian J; Chinnery, Patrick F
To investigate the possibility of auditory dysfunction in patients with Leber hereditary optic neuropathy (LHON). We prospectively recruited 10 affected patients from the north-east of England harbouring one of the three primary mitochondrial LHON mutations (3460G>A n = 3, 11778G>A n = 5 and 14484T>C n = 2). A detailed auditory history was taken and they were asked to complete a validated hearing questionnaire. Each patient then underwent a comprehensive topographic neuroauditory assessment to evaluate both middle- and inner-ear functions and the integrity of the brainstem auditory pathways. We found no evidence of cochlear nerve dysfunction or abnormalities of the central brainstem auditory pathways in our LHON cohort and five patients had completely normal hearing tests. The remainder had mild conductive hearing loss from childhood ear infections and/or high-frequency sensorineural hearing loss from previous noise injury. Although further studies are required to confirm our findings, auditory dysfunction as a result of a primary LHON mutation is probably uncommon.
Joshua R Gold
Full Text Available The brain displays a remarkable capacity for both widespread and region-specific modifications in response to environmental challenges, with adaptive processes bringing about the reweighting of connections in neural networks putatively required for optimising performance and behaviour. As an avenue for investigation, studies centred around changes in the mammalian auditory system, extending from the brainstem to the cortex, have revealed a plethora of mechanisms that operate in the context of sensory disruption after insult, be it lesion-, noise trauma, drug-, or age-related. Of particular interest in recent work are those aspects of auditory processing which, after sensory disruption, change at multiple – if not all – levels of the auditory hierarchy. These include changes in excitatory, inhibitory and neuromodulatory networks, consistent with theories of homeostatic plasticity; functional alterations in gene expression and in protein levels; as well as broader network processing effects with cognitive and behavioural implications. Nevertheless, there abounds substantial debate regarding which of these processes may only be sequelae of the original insult, and which may, in fact, be maladaptively compelling further degradation of the organism’s competence to cope with its disrupted sensory context. In this review, we aim to examine how the mammalian auditory system responds in the wake of particular insults, and to disambiguate how the changes that develop might underlie a correlated class of phantom disorders, including tinnitus and hyperacusis, which putatively are brought about through maladaptive neuroplastic disruptions to auditory networks governing the spatial and temporal processing of acoustic sensory information.
Joseph L. Regan
Full Text Available Summary: Colon cancer is a heterogeneous tumor driven by aÂ subpopulation of cancer stem cells (CSCs. To study CSCs in colon cancer, we used limiting dilution spheroid and serial xenotransplantation assays to functionally define the frequency of CSCs in a panel of patient-derived cancer organoids. These studies demonstrated cancer organoids to be enriched for CSCs, which varied in frequency between tumors. Whole-transcriptome analysis identified WNT and Hedgehog signaling components to be enhanced in CSC-enriched tumors and in aldehyde dehydrogenase (ALDH-positive CSCs. Canonical GLI-dependent Hedgehog signaling is a negative regulator of WNT signaling in normal intestine and intestinal tumors. Here, we show that Hedgehog signaling inÂ colon CSCs is autocrine SHH-dependent, non-canonicalÂ PTCH1 dependent, and GLI independent. InÂ addition, using small-molecule inhibitors and RNAi against SHH-palmitoylating Hedgehog acyltransferase (HHAT, we demonstrate that non-canonical Hedgehog signaling is a positive regulator of WNT signaling and required for colon CSC survival. : Colon cancer is a heterogeneous tumor driven by a subpopulation(s of therapy-resistant cancer stem cells (CSCs. Regan etÂ al. use 3D culture models to demonstrate that CSC survival is regulated by non-canonical, SHH-dependent, PTCH1-dependent Hedgehog signaling, which acts as a positive regulator of WNT signaling to block CSC differentiation. Keywords: WNT pathway, non-canonical Hedgehog signaling, cancer stem cell, colon cancer, cancer organoid, PTCH1, HHAT, SHH
Loo, Jenny Hooi Yin; Rosen, Stuart; Bamiou, Doris-Eva
Children with auditory processing disorder (APD) typically present with "listening difficulties,"' including problems understanding speech in noisy environments. The authors examined, in a group of such children, whether a 12-week computer-based auditory training program with speech material improved the perception of speech-in-noise test performance, and functional listening skills as assessed by parental and teacher listening and communication questionnaires. The authors hypothesized that after the intervention, (1) trained children would show greater improvements in speech-in-noise perception than untrained controls; (2) this improvement would correlate with improvements in observer-rated behaviors; and (3) the improvement would be maintained for at least 3 months after the end of training. This was a prospective randomized controlled trial of 39 children with normal nonverbal intelligence, ages 7 to 11 years, all diagnosed with APD. This diagnosis required a normal pure-tone audiogram and deficits in at least two clinical auditory processing tests. The APD children were randomly assigned to (1) a control group that received only the current standard treatment for children diagnosed with APD, employing various listening/educational strategies at school (N = 19); or (2) an intervention group that undertook a 3-month 5-day/week computer-based auditory training program at home, consisting of a wide variety of speech-based listening tasks with competing sounds, in addition to the current standard treatment. All 39 children were assessed for language and cognitive skills at baseline and on three outcome measures at baseline and immediate postintervention. Outcome measures were repeated 3 months postintervention in the intervention group only, to assess the sustainability of treatment effects. The outcome measures were (1) the mean speech reception threshold obtained from the four subtests of the listening in specialized noise test that assesses sentence perception in
Hoffmann, Lukas A; Kelly, Conor W; Nicholson, David A; Sober, Samuel J
Experimental manipulations of sensory feedback during complex behavior have provided valuable insights into the computations underlying motor control and sensorimotor plasticity(1). Consistent sensory perturbations result in compensatory changes in motor output, reflecting changes in feedforward motor control that reduce the experienced feedback error. By quantifying how different sensory feedback errors affect human behavior, prior studies have explored how visual signals are used to recalibrate arm movements(2,3) and auditory feedback is used to modify speech production(4-7). The strength of this approach rests on the ability to mimic naturalistic errors in behavior, allowing the experimenter to observe how experienced errors in production are used to recalibrate motor output. Songbirds provide an excellent animal model for investigating the neural basis of sensorimotor control and plasticity(8,9). The songbird brain provides a well-defined circuit in which the areas necessary for song learning are spatially separated from those required for song production, and neural recording and lesion studies have made significant advances in understanding how different brain areas contribute to vocal behavior(9-12). However, the lack of a naturalistic error-correction paradigm - in which a known acoustic parameter is perturbed by the experimenter and then corrected by the songbird - has made it difficult to understand the computations underlying vocal learning or how different elements of the neural circuit contribute to the correction of vocal errors(13). The technique described here gives the experimenter precise control over auditory feedback errors in singing birds, allowing the introduction of arbitrary sensory errors that can be used to drive vocal learning. Online sound-processing equipment is used to introduce a known perturbation to the acoustics of song, and a miniaturized headphones apparatus is used to replace a songbird's natural auditory feedback with the
Röttinger, Eric; DuBuc, Timothy Q.; Amiel, Aldine R.; Martindale, Mark Q.
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 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. PMID:25979707
Młynarski, Wiktor; McDermott, Josh H
Interaction with the world requires an organism to transform sensory signals into representations in which behaviorally meaningful properties of the environment are made explicit. These representations are derived through cascades of neuronal processing stages in which neurons at each stage recode the output of preceding stages. Explanations of sensory coding may thus involve understanding how low-level patterns are combined into more complex structures. To gain insight into such midlevel representations for sound, we designed a hierarchical generative model of natural sounds that learns combinations of spectrotemporal features from natural stimulus statistics. In the first layer, the model forms a sparse convolutional code of spectrograms using a dictionary of learned spectrotemporal kernels. To generalize from specific kernel activation patterns, the second layer encodes patterns of time-varying magnitude of multiple first-layer coefficients. When trained on corpora of speech and environmental sounds, some second-layer units learned to group similar spectrotemporal features. Others instantiate opponency between distinct sets of features. Such groupings might be instantiated by neurons in the auditory cortex, providing a hypothesis for midlevel neuronal computation.
He, Wenxin; Ding, Xiuyong; Zhang, Ruxiang; Chen, Jing; Zhang, Daoxing; Wu, Xihong
It is still a difficult clinical issue to decide whether a patient is a suitable candidate for a cochlear implant and to plan postoperative rehabilitation, especially for some special cases, such as auditory neuropathy. A partial solution to these problems is to preoperatively evaluate the functional integrity of the auditory neural pathways. For evaluating the strength of phase-locking of auditory neurons, which was not reflected in previous methods using electrically evoked auditory brainstem response (EABR), a new method for recording phase-locking related auditory responses to electrical stimulation, called the electrically evoked frequency-following response (EFFR), was developed and evaluated using guinea pigs. The main objective was to assess feasibility of the method by testing whether the recorded signals reflected auditory neural responses or artifacts. The results showed the following: 1) the recorded signals were evoked by neuron responses rather than by artifact; 2) responses evoked by periodic signals were significantly higher than those evoked by the white noise; 3) the latency of the responses fell in the expected range; 4) the responses decreased significantly after death of the guinea pigs; and 5) the responses decreased significantly when the animal was replaced by an electrical resistance. All of these results suggest the method was valid. Recording obtained using complex tones with a missing fundamental component and using pure tones with various frequencies were consistent with those obtained using acoustic stimulation in previous studies.
Kremer, Kimberly N.; Clift, Ian C.; Miamen, Alexander G.; Bamidele, Adebowale O.; Qian, Nan-Xin; Humphreys, Troy D.; Hedin, Karen E.
The CXCR4 chemokine receptor is a G protein-coupled receptor (GPCR) that signals in T lymphocytes by forming a heterodimer with the T cell antigen receptor (TCR). CXCR4 and TCR functions are consequently highly cross-regulated, affecting T cell immune activation, cytokine secretion, and T cell migration. The CXCR4-TCR heterodimer stimulates T cell migration and activation of the ERK MAP kinase and downstream AP-1-dependent cytokine transcription in response to SDF-1, the sole chemokine ligand of CXCR4. These responses require Gi-type G proteins as well as TCR ITAM domains and the ZAP-70 tyrosine kinase, thus indicating that the CXCR4-TCR heterodimer signals to integrate GPCR-associated and TCR-associated signaling molecules in response to SDF-1. Yet, the phospholipase C (PLC) isozymes responsible for coupling the CXCR4-TCR heterodimer to distinct downstream cellular responses are incompletely characterized. Here, we demonstrate that PLC activity is required for SDF-1 to induce ERK activation, migration, and CXCR4 endocytosis in human T cells. SDF-1 signaling via the CXCR4-TCR heterodimer uses PLC-β3 to activate the Ras-ERK pathway and increase intracellular Ca2+ concentrations, while PLC-γ1 is dispensable for these outcomes. In contrast, PLC-γ1, but not PLC-β3, is required for SDF-1-mediated migration, via a mechanism independent of LAT. These results increase understanding of the signaling mechanisms employed by the CXCR4-TCR heterodimer, characterize new roles for PLC-β3 and PLC-γ1 in T cells, and suggest that multiple PLCs may also be activated downstream of other chemokine receptors in order to distinctly regulate migration versus other signaling functions. PMID:21705626
The article summarizes information on assistive devices (hearing aids, cochlear implants, tactile aids, visual aids) and rehabilitation procedures (auditory training, speechreading, cued speech, and speech production) to aid the auditory learning of the hearing impaired.(DB)
Bell, Brittany A; Phan, Mimi L; Vicario, David S
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. Copyright © 2015 the American Physiological Society.
Osman, Homira; Sullivan, Jessica R
The objectives of this study were to determine (a) whether school-age children with typical hearing demonstrate poorer auditory working memory performance in multitalker babble at degraded signal-to-noise ratios than in quiet; and (b) whether the amount of cognitive demand of the task contributed to differences in performance in noise. It was hypothesized that stressing the working memory system with the presence of noise would impede working memory processes in real time and result in poorer working memory performance in degraded conditions. Twenty children with typical hearing between 8 and 10 years old were tested using 4 auditory working memory tasks (Forward Digit Recall, Backward Digit Recall, Listening Recall Primary, and Listening Recall Secondary). Stimuli were from the standardized Working Memory Test Battery for Children. Each task was administered in quiet and in 4-talker babble noise at 0 dB and -5 dB signal-to-noise ratios. Children's auditory working memory performance was systematically decreased in the presence of multitalker babble noise compared with quiet. Differences between low-complexity and high-complexity tasks were observed, with children performing more poorly on tasks with greater storage and processing demands. There was no interaction between noise and complexity of task. All tasks were negatively impacted similarly by the addition of noise. Auditory working memory performance was negatively impacted by the presence of multitalker babble noise. Regardless of complexity of task, noise had a similar effect on performance. These findings suggest that the addition of noise inhibits auditory working memory processes in real time for school-age children.
Lunney, David; Morrison, Robert C.
Our research group has been working for several years on the development of auditory alternatives to visual graphs, primarily in order to give blind science students and scientists access to instrumental measurements. In the course of this work we have tried several modes for auditory presentation of data: synthetic speech, tones of varying pitch, complex waveforms, electronic music, and various non-musical sounds. Our most successful translation of data into sound has been presentation of infrared spectra as musical patterns. We have found that if the stick spectra of two compounds are visibly different, their musical patterns will be audibly different. Other possibilities for auditory presentation of data are also described, among them listening to Fourier transforms of spectra, and encoding data in complex waveforms (including synthetic speech).
Chen, Sufen; Sussman, Elyse S.
The purpose of the study was to test the hypothesis that sound context modulates the magnitude of auditory distraction, indexed by behavioral and electrophysiological measures. Participants were asked to identify tone duration, while irrelevant changes occurred in tone frequency, tone intensity, and harmonic structure. Frequency deviants were randomly intermixed with standards (Uni-Condition), with intensity deviants (Bi-Condition), and with both intensity and complex deviants (Tri-Condition). Only in the Tri-Condition did the auditory distraction effect reflect the magnitude difference among the frequency and intensity deviants. The mixture of the different types of deviants in the Tri-Condition modulated the perceived level of distraction, demonstrating that the sound context can modulate the effect of deviance level on processing irrelevant acoustic changes in the environment. These findings thus indicate that perceptual contrast plays a role in change detection processes that leads to auditory distraction. PMID:23886958
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.
Borra, Tobias; Versnel, Huib; Kemner, Chantal; van Opstal, A John; van Ee, Raymond
After hearing a tone, the human auditory system becomes more sensitive to similar tones than to other tones. Current auditory models explain this phenomenon by a simple bandpass attention filter. Here, we demonstrate that auditory attention involves multiple pass-bands around octave-related frequencies above and below the cued tone. Intriguingly, this "octave effect" not only occurs for physically presented tones, but even persists for the missing fundamental in complex tones, and for imagined tones. Our results suggest neural interactions combining octave-related frequencies, likely located in nonprimary cortical regions. We speculate that this connectivity scheme evolved from exposure to natural vibrations containing octave-related spectral peaks, e.g., as produced by vocal cords.
Shen, Lu-Lu; Du, Min; Lin, Xing-Feng; Cai, Ting; Wang, Da-Yong
To investigate the interaction between the genes required for the functions of AWA olfactory neuron and insulin/IGF signaling in regulating the longevity of nematode Caenorhabditis elegans (C. elegans). The mutants that had loss-of-function mutation of the genes required for AWA, AWC, ASE, and AFD sensory neurons were employed. Lifespan, the speed of pharynx pumping, the intestinal autofluorescence, the dauer formation, and the brood size were examined. Rescue experiments were performed to confirm the role of the genes required for the functions of AWA neuron in regulating lifespan. Moreover, genetic interactions between genes required for the functions of AWA neuron and insulin/IGF signaling were investigated. Mutations of odr-7, odr-2, and odr-3 genes required for the functions of AWA neuron significantly increased the mean lifespan of nematodes and slowed the accumulation of intestinal autofluorescence. Besides, these mutations were closely associated with higher pumping rates during aging. However, mutation of odr-7, odr-2, or odr-3 did not obviously affect the brood size or the dauer formation, and the regulation of longevity by odr-7, odr-2, and odr-3 was temperature-independent. In contrast, mutations of genes required for the functions of ASE, AWC, and AFD sensory neurons did not influence the nematode lifespan. Moreover, expression of odr-7, odr-2 and odr-3 in AWA neuron could completely or largely restore the altered lifespan in odr-7, odr-2 and odr-3 mutants. Furthermore, genetic interaction assay demonstrated that the extended lifespan in odr-7 mutant could be suppressed by daf-16 mutation and enhanced by daf-2 or age-1 mutation, whereas mev-1 and pha-4 were not required for the long lifespan of odr-7 mutant. The genes required for the function of AWA sensory neuron could regulate the nematode longevity in an insulin/IGF signaling-dependent fashion in C. elegans.
Salimpoor, Valorie N; van den Bosch, Iris; Kovacevic, Natasa; McIntosh, Anthony Randal; Dagher, Alain; Zatorre, Robert J
... unheard music in an auction paradigm. Importantly, the auditory cortices, amygdala, and ventromedial prefrontal regions showed increased activity during listening conditions requiring valuation, but did not predict reward value...
Katharina S. Rufener
Full Text Available Neural oscillations in the gamma range are the dominant rhythmic activation pattern in the human auditory cortex. These gamma oscillations are functionally relevant for the processing of rapidly changing acoustic information in both speech and non-speech sounds. Accordingly, there is a tight link between the temporal resolution ability of the auditory system and inherent neural gamma oscillations. Transcranial random noise stimulation (tRNS has been demonstrated to specifically increase gamma oscillation in the human auditory cortex. However, neither the physiological mechanisms of tRNS nor the behavioral consequences of this intervention are completely understood. In the present study we stimulated the human auditory cortex bilaterally with tRNS while EEG was continuously measured. Modulations in the participants’ temporal and spectral resolution ability were investigated by means of a gap detection task and a pitch discrimination task. Compared to sham, auditory tRNS increased the detection rate for near-threshold stimuli in the temporal domain only, while no such effect was present for the discrimination of spectral features. Behavioral findings were paralleled by reduced peak latencies of the P50 and N1 component of the auditory event-related potentials (ERP indicating an impact on early sensory processing. The facilitating effect of tRNS was limited to the processing of near-threshold stimuli while stimuli clearly below and above the individual perception threshold were not affected by tRNS. This non-linear relationship between the signal-to-noise level of the presented stimuli and the effect of stimulation further qualifies stochastic resonance (SR as the underlying mechanism of tRNS on auditory processing. Our results demonstrate a tRNS related improvement in acoustic perception of time critical auditory information and, thus, provide further indices that auditory tRNS can amplify the resonance frequency of the auditory system.
Liu, Po-Pu; von Dahl, Caroline C; Klessig, Daniel F
Systemic acquired resistance (SAR) is a state of heightened defense to a broad spectrum of pathogens that is activated throughout a plant following local infection. Development of SAR requires the translocation of one or more mobile signals from the site of infection through the vascular system to distal (systemic) tissues. The first such signal identified was methyl salicylate (MeSA) in tobacco (Nicotiana tabacum). Subsequent studies demonstrated that MeSA also serves as a SAR signal in Arabidopsis (Arabidopsis thaliana) and potato (Solanum tuberosum). By contrast, another study suggested that MeSA is not required for SAR in Arabidopsis and raised questions regarding its signaling role in tobacco. Differences in experimental design, including the developmental age of the plants, the light intensity, and/or the strain of bacterial pathogen, were proposed to explain these conflicting results. Here, we demonstrate that the length of light exposure that plants receive after the primary infection determines the extent to which MeSA is required for SAR signaling. When the primary infection occurred late in the day and as a result infected plants received very little light exposure before entering the night/dark period, MeSA and its metabolizing enzymes were essential for SAR development. In contrast, when infection was done in the morning followed by 3.5 h or more of exposure to light, SAR developed in the absence of MeSA. However, MeSA was generally required for optimal SAR development. In addition to resolving the conflicting results concerning MeSA and SAR, this study underscores the importance of environmental factors on the plant's response to infection.
Liu, Po-Pu; von Dahl, Caroline C.; Klessig, Daniel F.
Systemic acquired resistance (SAR) is a state of heightened defense to a broad spectrum of pathogens that is activated throughout a plant following local infection. Development of SAR requires the translocation of one or more mobile signals from the site of infection through the vascular system to distal (systemic) tissues. The first such signal identified was methyl salicylate (MeSA) in tobacco (Nicotiana tabacum). Subsequent studies demonstrated that MeSA also serves as a SAR signal in Arabidopsis (Arabidopsis thaliana) and potato (Solanum tuberosum). By contrast, another study suggested that MeSA is not required for SAR in Arabidopsis and raised questions regarding its signaling role in tobacco. Differences in experimental design, including the developmental age of the plants, the light intensity, and/or the strain of bacterial pathogen, were proposed to explain these conflicting results. Here, we demonstrate that the length of light exposure that plants receive after the primary infection determines the extent to which MeSA is required for SAR signaling. When the primary infection occurred late in the day and as a result infected plants received very little light exposure before entering the night/dark period, MeSA and its metabolizing enzymes were essential for SAR development. In contrast, when infection was done in the morning followed by 3.5 h or more of exposure to light, SAR developed in the absence of MeSA. However, MeSA was generally required for optimal SAR development. In addition to resolving the conflicting results concerning MeSA and SAR, this study underscores the importance of environmental factors on the plant’s response to infection. PMID:22021417
Robert J Thoma
Full Text Available 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 on-set and off-set of AVH during fMRI scanning. When a general linear model (GLM was used to compare BOLD 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 extra-nuclear white matter. In an effort to identify AVH-related networks, the raw data were also processed using independent component analyses (ICA. 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 with the pattern of AVH-on versus AVH-off. The ICA also identified two additional networks (occipital-temporal and medial pre-frontal, 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.
Mizutani, Tatsuaki; Neugebauer, Nina; Putz, Eva M.; Moritz, Nadine; Simma, Olivia; Zebedin-Brandl, Eva; Gotthardt, Dagmar; Warsch, Wolfgang; Eckelhart, Eva; Kantner, Hans-Peter; Kalinke, Ulrich; Lienenklaus, Stefan; Weiss, Siegfried; Strobl, Birgit; Müller, Mathias
Mice with an impaired Type I interferon (IFN) signaling (IFNAR1- and IFNβ-deficient mice) display an increased susceptibility toward v-ABL-induced B-cell leukemia/lymphoma. The enhanced leukemogenesis in the absence of an intact Type I IFN signaling is caused by alterations within the tumor environment. Deletion of Ifnar1 in tumor cells (as obtained in Ifnar1f/f CD19-Cre mice) failed to impact on disease latency or type. In line with this observation, the initial transformation and proliferat...
Full Text Available Relying on the mechanism of bat’s echolocation system, a bioinspired electronic device has been developed to investigate the cortical activity of mammals in response to auditory sensorial stimuli. By means of implanted electrodes, acoustical information about the external environment generated by a biomimetic system and converted in electrical signals was delivered to anatomically selected structures of the auditory pathway. Electrocorticographic recordings showed that cerebral activity response is highly dependent on the information carried out by ultrasounds and is frequency-locked with the signal repetition rate. Frequency analysis reveals that delta and beta rhythm content increases, suggesting that sensorial information is successfully transferred and integrated. In addition, principal component analysis highlights how all the stimuli generate patterns of neural activity which can be clearly classified. The results show that brain response is modulated by echo signal features suggesting that spatial information sent by biomimetic sonar is efficiently interpreted and encoded by the auditory system. Consequently, these results give new perspective in artificial environmental perception, which could be used for developing new techniques useful in treating pathological conditions or influencing our perception of the surroundings.
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...
Darvas, Martin; Fadok, Jonathan P.; Palmiter, Richard D.
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…
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; Sears, Rosalie C.; Clarke, Alan R.; Frame, Margaret C.; Sansom, Owen J.
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
Castellano-Muñoz, Manuel; Schnee, Michael E; Ricci, Anthony J
Hair cells from auditory and vestibular systems transmit continuous sound and balance information to the central nervous system through the release of synaptic vesicles at ribbon synapses. The high activity experienced by hair cells requires a unique mechanism to sustain recruitment and replenishment of synaptic vesicles for continuous release. Using pre- and postsynaptic electrophysiological recordings, we explored the potential contribution of calcium-induced calcium release (CICR) in modulating the recruitment of vesicles to auditory hair cell ribbon synapses. Pharmacological manipulation of CICR with agents targeting endoplasmic reticulum calcium stores reduced both spontaneous postsynaptic multiunit activity and the frequency of excitatory postsynaptic currents (EPSCs). Pharmacological treatments had no effect on hair cell resting potential or activation curves for calcium and potassium channels. However, these drugs exerted a reduction in vesicle release measured by dual-sine capacitance methods. In addition, calcium substitution by barium reduced release efficacy by delaying release onset and diminishing vesicle recruitment. Together these results demonstrate a role for calcium stores in hair cell ribbon synaptic transmission and suggest a novel contribution of CICR in hair cell vesicle recruitment. We hypothesize that calcium entry via calcium channels is tightly regulated to control timing of vesicle fusion at the synapse, whereas CICR is used to maintain a tonic calcium signal to modulate vesicle trafficking. Copyright © 2016 the American Physiological Society.
Cristina F.B. Murphy
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.
Müller, Nadia; Keil, Julian; Obleser, Jonas; Schulz, Hannah; Grunwald, Thomas; Bernays, René-Ludwig; Huppertz, Hans-Jürgen; Weisz, Nathan
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. Copyright © 2013 Elsevier Inc. All rights reserved.
Fitzpatrick, Douglas C; Roberts, Jason M; Kuwada, Shigeyuki; Kim, Duck O; Filipovic, Blagoje
Processing dynamic changes in the stimulus stream is a major task for sensory systems. In the auditory system, an increase in the temporal integration window between the inferior colliculus (IC) and auditory cortex is well known for monaural signals such as amplitude modulation, but a similar increase with binaural signals has not been demonstrated. To examine the limits of binaural temporal processing at these brain levels, we used the binaural beat stimulus, which causes a fluctuating interaural phase difference, while recording from neurons in the unanesthetized rabbit. We found that the cutoff frequency for neural synchronization to the binaural beat frequency (BBF) decreased between the IC and auditory cortex, and that this decrease was associated with an increase in the group delay. These features indicate that there is an increased temporal integration window in the cortex compared to the IC, complementing that seen with monaural signals. Comparable measurements of responses to amplitude modulation showed that the monaural and binaural temporal integration windows at the cortical level were quantitatively as well as qualitatively similar, suggesting that intrinsic membrane properties and afferent synapses to the cortical neurons govern the dynamic processing. The upper limits of synchronization to the BBF and the band-pass tuning characteristics of cortical neurons are a close match to human psychophysics.
David J Brown
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.
Harding, Molly J; Nechiporuk, Alex V
Many morphogenetic movements during development require the formation of transient intermediates called rosettes. Within rosettes, cells are polarized with apical ends constricted towards the rosette center and nuclei basally displaced. Whereas the polarity and cytoskeletal machinery establishing these structures has been extensively studied, the extracellular cues and intracellular signaling cascades that promote their formation are not well understood. We examined how extracellular Fibroblast growth factor (Fgf) signals regulate rosette formation in the zebrafish posterior lateral line primordium (pLLp), a group of ∼100 cells that migrates along the trunk during embryonic development to form the lateral line mechanosensory system. During migration, the pLLp deposits rosettes from the trailing edge, while cells are polarized and incorporated into nascent rosettes in the leading region. Fgf signaling was previously shown to be crucial for rosette formation in the pLLp. We demonstrate that activation of Fgf receptor (Fgfr) induces intracellular Ras-MAPK, which is required for apical constriction and rosette formation in the pLLp. Inhibiting Fgfr-Ras-MAPK leads to loss of apically localized Rho-associated kinase (Rock) 2a, which results in failed actomyosin cytoskeleton activation. Using mosaic analyses, we show that a cell-autonomous Ras-MAPK signal is required for apical constriction and Rock2a localization. We propose a model whereby activated Fgfr signals through Ras-MAPK to induce apical localization of Rock2a in a cell-autonomous manner, activating the actomyosin network to promote apical constriction and rosette formation in the pLLp. This mechanism presents a novel cellular strategy for driving cell shape changes.
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.
Ghosh, Abhishek; Rideout, Elizabeth J; Grewal, Savraj S
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.
de Villers-Sidani, Etienne; Merzenich, Michael M
The rodent auditory cortex has provided a particularly useful model for studying cortical plasticity phenomenology and mechanisms, both in infant and in adult animal models. Much of our initial understanding of the neurological processes underlying learning-induced changes in the cortex stems from the early exploitation of this model. More recent studies have provided a rich and elaborate demonstration of the "rules" governing representational plasticity induced during the critical period (CP) and in the longer post-CP "adult" plasticity epoch. These studies have also contributed importantly to the application of these "rules" to the development of practical training tools designed to improve the functional capacities of the auditory, language, and reading capacities of both children with developmental impairments and adults with acquired impairments in the auditory/aural speed and related cognitive domains. Using age as a connecting thread, we review recent studies performed in the rat primary auditory cortex (A1) that have provided further insight into the role of sensory experience in the shaping auditory signal representations, and into their possible role in shaping the machinery that regulates "adult" plasticity in A1. With this background, the role of auditory training in the remediation of auditory processing impairments is briefly discussed. Copyright © 2011 Elsevier B.V. All rights reserved.
Lee, Hyoung Yool; Back, Kyoungwhan
Melatonin influences plant innate immunity through the mitogen-activated protein kinase (MAPK) pathway. However, the most upstream MAPK component in melatonin signaling and the dependence of generation of a reactive oxygen species (ROS) burst on melatonin synthesis and signaling remain unclear. In this study, treatment of several mekk (alias mapkkk)-knockout Arabidopsis mutants with melatonin revealed that the MAPKKK3 and OXI1 (oxidative signal-inducible1) kinases are responsible for triggering melatonin-induced defense signaling pathways. In addition, melatonin induction upon infection with the avirulent pathogen Pseudomonas syringae DC3000 (avrRpt2) was independent of H2 O2 and NO individually, but dependent on the combination of H2 O2 and NO. Moreover, melatonin-mediated induction of the expression of defense-related genes, such as PR1 and ICS1, was not altered in the H2 O2 -deficient rbohD/F-knockout mutant cotreated with an NO scavenger, indicating that melatonin functions downstream of the ROS and NO burst. Collectively, the data indicate that melatonin-mediated induction of an innate immune response requires multiple signaling molecules and activation of MAPKKK3 and OXI1, followed by triggering of downstream MAPK cascades, such as MAPK3 and MAPK6. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Sui, Lina, E-mail: email@example.com [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)
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.
Full Text Available Embryo homing and implantation occur within a crypt (implantation chamber at the antimesometrial (AM pole along the uterus. The mechanism by which this is achieved is not known. Here, we show that villi-like epithelial projections from the main uterine lumen toward the AM pole at regularly spaced intervals that form crypts for embryo implantation were disrupted in mice with uterine loss or gain of function of Wnt5a, or loss of function of both Ror1 and Ror2. This disruption of Wnt5a-ROR signaling resulted in disorderly epithelial projections, crypt formation, embryo spacing, and impaired implantation. These early disturbances under abnormal Wnt5a-ROR signaling were reflected in adverse late pregnancy events, including defective decidualization and placentation, ultimately leading to compromised pregnancy outcomes. This study presents deeper insight regarding the formation of organized epithelial projections for crypt formation and embryo implantation for pregnancy success.
Blom, Jan Dirk; Sommer, Iris E. C.
Introduction: The literature on the possible neurobiologic correlates of auditory hallucinations is expanding rapidly. For an adequate understanding and linking of this emerging knowledge, a clear and uniform nomenclature is a prerequisite. The primary purpose of the present article is to provide an
Lankford, James E.; Meinke, Deanna K.; Flamme, Gregory A.; Finan, Donald S.; Stewart, Michael; Tasko, Stephen; Murphy, William J.
Objective To characterize the impulse noise exposure and auditory risk for air rifle users for both youth and adults. Design Acoustic characteristics were examined and the auditory risk estimates were evaluated using contemporary damage-risk criteria for unprotected adult listeners and the 120-dB peak limit and LAeq75 exposure limit suggested by the World Health Organization (1999) for children. Study sample Impulses were generated by 9 pellet air rifles and 1 BB air rifle. Results None of the air rifles generated peak levels that exceeded the 140 dB peak limit for adults and 8 (80%) exceeded the 120 dB peak SPL limit for youth. In general, for both adults and youth there is minimal auditory risk when shooting less than 100 unprotected shots with pellet air rifles. Air rifles with suppressors were less hazardous than those without suppressors and the pellet air rifles with higher velocities were generally more hazardous than those with lower velocities. Conclusion To minimize auditory risk, youth should utilize air rifles with an integrated suppressor and lower velocity ratings. Air rifle shooters are advised to wear hearing protection whenever engaging in shooting activities in order to gain self-efficacy and model appropriate hearing health behaviors necessary for recreational firearm use. PMID:26840923
Silva, Magali Aparecida Orate Menezes da; Piatto, Vânia Belintani; Maniglia, Jose Victor
Mutations in the otoferlin gene are responsible for auditory neuropathy. To investigate the prevalence of mutations in the mutations in the otoferlin gene in patients with and without auditory neuropathy. This original cross-sectional case study evaluated 16 index cases with auditory neuropathy, 13 patients with sensorineural hearing loss, and 20 normal-hearing subjects. DNA was extracted from peripheral blood leukocytes, and the mutations in the otoferlin gene sites were amplified by polymerase chain reaction/restriction fragment length polymorphism. The 16 index cases included nine (56%) females and seven (44%) males. The 13 deaf patients comprised seven (54%) males and six (46%) females. Among the 20 normal-hearing subjects, 13 (65%) were males and seven were (35%) females. Thirteen (81%) index cases had wild-type genotype (AA) and three (19%) had the heterozygous AG genotype for IVS8-2A-G (intron 8) mutation. The 5473C-G (exon 44) mutation was found in a heterozygous state (CG) in seven (44%) index cases and nine (56%) had the wild-type allele (CC). Of these mutants, two (25%) were compound heterozygotes for the mutations found in intron 8 and exon 44. All patients with sensorineural hearing loss and normal-hearing individuals did not have mutations (100%). There are differences at the molecular level in patients with and without auditory neuropathy. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.
Reported is the case study of a boy with severe auditory dyslexia who received remedial treatment from the age of four and progressed through courses at a technical college and a 3-year apprenticeship course in mechanics by the age of eighteen. (IM)
... Auditory Neuropathy Autism Spectrum Disorder: Communication Problems in Children Dysphagia Quick Statistics About Voice, Speech, Language Speech and Language Developmental Milestones What Is Voice? What Is Speech? What Is Language? ... communication provides better outcomes for children with cochlear implants University of Texas at Dallas ...
Duncan, Jeremy S; Fritzsch, Bernd
We review the molecular basis of auditory development and evolution. We propose that the auditory periphery (basilar papilla, organ of Corti) evolved by transforming a newly created and redundant vestibular (gravistatic) endorgan into a sensory epithelium that could respond to sound instead of gravity. Evolution altered this new epithelia's mechanoreceptive properties through changes of hair cells, positioned the epithelium in a unique position near perilymphatic space to extract sound moving between the round and the oval window, and transformed its otolith covering into a tympanic membrane. Another important step in the evolution of an auditory system was the evolution of a unique set of "auditory neurons" that apparently evolved from vestibular neurons. Evolution of mammalian auditory (spiral ganglion) neurons coincides with GATA3 being a transcription factor found selectively in the auditory afferents. For the auditory information to be processed, the CNS required a dedicated center for auditory processing, the auditory nuclei. It is not known whether the auditory nucleus is ontogenetically related to the vestibular or electroreceptive nuclei, two sensory systems found in aquatic but not in amniotic vertebrates, or a de-novo formation of the rhombic lip in line with other novel hindbrain structures such as pontine nuclei. Like other novel hindbrain structures, the auditory nuclei express exclusively the bHLH gene Atoh1, and loss of Atoh1 results in loss of most of this nucleus in mice. Only after the basilar papilla, organ of Corti evolved could efferent neurons begin to modulate their activity. These auditory efferents most likely evolved from vestibular efferent neurons already present. The most simplistic interpretation of available data suggest that the ear, sensory neurons, auditory nucleus, and efferent neurons have been transformed by altering the developmental genetic modules necessary for their development into a novel direction conducive for sound
Otophysine fishes have a series of bones, the Weberian ossicles, which acoustically couple the swimbladder to the inner ear. These fishes have evolved a diversity of sound-generating organs and acoustic signals, although some species, such as the goldfish, are not known to be vocal. Utilizing a recently developed auditory brainstem response (ABR)-recording technique, the auditory sensitivities of representatives of seven families from all four otophysine orders were investigated and compared to the spectral content of their vocalizations. All species examined detect tone bursts from 100 Hz to 5 kHz, but ABR-audiograms revealed major differences in auditory sensitivities, especially at higher frequencies (>1 kHz) where thresholds differed by up to 50 dB. These differences showed no apparent correspondence to the ability to produce sounds (vocal versus non-vocal species) or to the spectral content of species-specific sounds. All fishes have maximum sensitivity between 400 Hz and 1,500 Hz, whereas the major portion of the energy of acoustic signals was in the frequency range of 100-400 Hz (swimbladder drumming sounds) and of 1-3 kHz (stridulatory sounds). Species producing stridulatory sounds exhibited better high-frequency hearing sensitivity (pimelodids, doradids), except for callichthyids, which had poorest hearing ability in this range. Furthermore, fishes emitting both low- and high-frequency sounds, such as pimelodid and doradid catfishes, did not possess two corresponding auditory sensitivity maxima. Based on these results it is concluded that selective pressures involved in the evolution of the Weberian apparatus and the design of vocal signals in otophysines were others (primarily predator or prey detection in quiet freshwater habitats) than those serving to optimize acoustical communication.
Hildebrandt, K Jannis; Benda, Jan; Hennig, R Matthias
Hearing in insects serves to gain information in the context of mate finding, predator avoidance or host localization. For these goals, the auditory pathways of insects represent the computational substrate for object recognition and localization. Before these higher level computations can be executed in more central parts of the nervous system, the signals need to be preprocessed in the auditory periphery. Here, we review peripheral preprocessing along four computational themes rather than discussing specific physiological mechanisms: (1) control of sensitivity by adaptation, (2) recoding of amplitude modulations of an acoustic signal into a labeled-line code (3) frequency processing and (4) conditioning for binaural processing. Along these lines, we review evidence for canonical computations carried out in the peripheral auditory pathway and show that despite the vast diversity of insect hearing, signal processing is governed by common computational motifs and principles.
Simon, Jonathan Z
Auditory objects, like their visual counterparts, are perceptually defined constructs, but nevertheless must arise from underlying neural circuitry. Using magnetoencephalography (MEG) recordings of the neural responses of human subjects listening to complex auditory scenes, we review studies that demonstrate that auditory objects are indeed neurally represented in auditory cortex. The studies use neural responses obtained from different experiments in which subjects selectively listen to one of two competing auditory streams embedded in a variety of auditory scenes. The auditory streams overlap spatially and often spectrally. In particular, the studies demonstrate that selective attentional gain does not act globally on the entire auditory scene, but rather acts differentially on the separate auditory streams. This stream-based attentional gain is then used as a tool to individually analyze the different neural representations of the competing auditory streams. The neural representation of the attended stream, located in posterior auditory cortex, dominates the neural responses. Critically, when the intensities of the attended and background streams are separately varied over a wide intensity range, the neural representation of the attended speech adapts only to the intensity of that speaker, irrespective of the intensity of the background speaker. This demonstrates object-level intensity gain control in addition to the above object-level selective attentional gain. Overall, these results indicate that concurrently streaming auditory objects, even if spectrally overlapping and not resolvable at the auditory periphery, are individually neurally encoded in auditory cortex, as separate objects. Copyright © 2014 Elsevier B.V. All rights reserved.
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.
Vassilakis, Pantelis N.; Kendall, Roger A.
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.
Sharma, Nanaocha; Longjam, Geeta; Schreiber, Gideon
Type I interferons serve as the first line of defense against pathogen invasion. Binding of IFNs to its receptors, IFNAR1 and IFNAR2, is leading to activation of the IFN response. To determine whether structural perturbations observed during binding are propagated to the cytoplasmic domain, multiple mutations were introduced into the transmembrane helix and its surroundings. Insertion of one to five alanine residues near either the N or C terminus of the transmembrane domain (TMD) likely promotes a rotation of 100° and a translation of 1.5 Å per added residue. Surprisingly, the added alanines had little effect on the binding affinity of IFN to the cell surface receptors, STAT phosphorylation, or gene induction. Similarly, substitution of the juxtamembrane residues of the TMD with alanines, or replacement of the TMD of IFNAR1 with that of IFNAR2, did not affect IFN binding or activity. Finally, only the addition of 10 serine residues (but not 2 or 4) between the extracellular domain of IFNAR1 and the TMD had some effect on signaling. Bioinformatic analysis shows a correlation between high sequence conservation of TMDs of cytokine receptors and the ability to transmit structural signals. Sequence conservation near the TMD of IFNAR1 is low, suggesting limited functional importance for this region. Our results suggest that IFN binding to the extracellular domains of IFNAR1 and IFNAR2 promotes proximity between the intracellular domains and that differential signaling is a function of duration of activation and affinity of binding rather than specific conformational changes transmitted from the outside to the inside of the cell. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
Sharma, Nanaocha; Longjam, Geeta; Schreiber, Gideon
Type I interferons serve as the first line of defense against pathogen invasion. Binding of IFNs to its receptors, IFNAR1 and IFNAR2, is leading to activation of the IFN response. To determine whether structural perturbations observed during binding are propagated to the cytoplasmic domain, multiple mutations were introduced into the transmembrane helix and its surroundings. Insertion of one to five alanine residues near either the N or C terminus of the transmembrane domain (TMD) likely promotes a rotation of 100° and a translation of 1.5 Å per added residue. Surprisingly, the added alanines had little effect on the binding affinity of IFN to the cell surface receptors, STAT phosphorylation, or gene induction. Similarly, substitution of the juxtamembrane residues of the TMD with alanines, or replacement of the TMD of IFNAR1 with that of IFNAR2, did not affect IFN binding or activity. Finally, only the addition of 10 serine residues (but not 2 or 4) between the extracellular domain of IFNAR1 and the TMD had some effect on signaling. Bioinformatic analysis shows a correlation between high sequence conservation of TMDs of cytokine receptors and the ability to transmit structural signals. Sequence conservation near the TMD of IFNAR1 is low, suggesting limited functional importance for this region. Our results suggest that IFN binding to the extracellular domains of IFNAR1 and IFNAR2 promotes proximity between the intracellular domains and that differential signaling is a function of duration of activation and affinity of binding rather than specific conformational changes transmitted from the outside to the inside of the cell. PMID:26679999
Hackam, David J.; Rotstein, Ori D.; Schreiber, Alan; Zhang, Wei-jian; Grinstein, Sergio
Phagocytosis of bacteria by macrophages and neutrophils is an essential component of host defense against infection. The mechanism whereby the interaction of opsonized particles with Fcγ receptors triggers the engulfment of opsonized particles remains incompletely understood, although activation of tyrosine kinases has been recognized as an early step. Recent studies in other systems have demonstrated that tyrosine kinases can in turn signal the activation of small GTPases of the ras superfamily. We therefore investigated the possible role of Rho in Fc receptor–mediated phagocytosis. To this end we microinjected J774 macrophages with C3 exotoxin from Clostridium botulinum, which ADP-ribosylates and inactivates Rho. C3 exotoxin induced the retraction of filopodia, the disappearance of focal complexes, and a global decrease in the F-actin content of J774 cells. In addition, these cells exhibited increased spreading and the formation of vacuolar structures. Importantly, inactivation of Rho resulted in the complete abrogation of phagocytosis. Inhibition of Fcγ receptor–mediated phagocytosis by C3 exotoxin was confirmed in COS cells, which become phagocytic upon transfection of the FcγRIIA receptor. Rho was found to be essential for the accumulation of phosphotyrosine and of F-actin around phagocytic cups and for Fcγ receptor–mediated Ca2+ signaling. The clustering of receptors in response to opsonin, an essential step in Fcγ-induced signaling, was the earliest event shown to be inhibited by C3 exotoxin. The effect of the toxin was specific, since clustering and internalization of transferrin receptors were unaffected by microinjection of C3. These data identify a role for small GTPases in Fcγ receptor–mediated phagocytosis by leukocytes. PMID:9294149
Krieger, Nancy S; Bushinsky, David A
Serum fibroblast growth factor 23 (FGF23) increases progressively in chronic kidney disease (CKD) and is associated with increased mortality. FGF23 is synthesized in osteoblasts and osteocytes; however, the factors regulating its production are not clear. Patients with CKD have decreased renal acid excretion leading to metabolic acidosis (MET). During MET, acid is buffered by bone with release of mineral calcium (Ca) and phosphate (P). MET increases intracellular Ca signaling and cyclooxygenase 2 (COX2)-induced prostaglandin production in the osteoblast, leading to decreased bone formation and increased bone resorption. We found that MET directly stimulates FGF23 in mouse bone organ cultures and primary osteoblasts. We hypothesized that MET increases FGF23 through similar pathways that lead to bone resorption. Neonatal mouse calvariae were incubated in neutral (NTL, pH = 7.44, Pco2 = 38 mmHg, [HCO3-] = 27 mM) or acid (MET, pH = 7.18, Pco2 = 37 mmHg, [HCO3-] = 13 mM) medium without or with 2-APB (50 μM), an inhibitor of intracellular Ca signaling or NS-398 (1 μM), an inhibitor of COX2. Each agent significantly inhibited MET stimulation of medium FGF23 protein and calvarial FGF23 RNA as well as bone resorption at 48 h. To exclude the potential contribution of MET-induced bone P release, we utilized primary calvarial osteoblasts. In these cells each agent inhibited MET stimulation of FGF23 RNA expression at 6 h. Thus stimulation of FGF23 by MET in mouse osteoblasts utilizes the same initial signaling pathways as MET-induced bone resorption. Therapeutic interventions directed toward correction of MET, especially in CKD, have the potential to not only prevent bone resorption but also lower FGF23 and perhaps decrease mortality. Copyright © 2017 the American Physiological Society.
Gutschalk, Alexander; Brandt, Tobias; Bartsch, Andreas; Jansen, Claudia
In contrast to lesions of the visual and somatosensory cortex, lesions of the auditory cortex are not associated with self-evident contralesional deficits. Only when two or more stimuli are presented simultaneously to the left and right, contralesional extinction has been observed after unilateral lesions of the auditory cortex. Because auditory extinction is also considered a sign of neglect, clinical separation of auditory neglect from deficits caused by lesions of the auditory cortex is challenging. Here, we directly compared a number of tests previously used for either auditory-cortex lesions or neglect in 29 controls and 27 patients suffering from unilateral auditory-cortex lesions, neglect, or both. The results showed that a dichotic-speech test revealed similar amounts of extinction for both auditory cortex lesions and neglect. Similar results were obtained for words lateralized by inter-aural time differences. Consistent extinction after auditory cortex lesions was also observed in a dichotic detection task. Neglect patients showed more general problems with target detection but no consistent extinction in the dichotic detection task. In contrast, auditory lateralization perception was biased toward the right in neglect but showed considerably less disruption by auditory cortex lesions. Lateralization of auditory-evoked magnetic fields in auditory cortex was highly correlated with extinction in the dichotic target-detection task. Moreover, activity in the right primary auditory cortex was somewhat reduced in neglect patients. The results confirm that auditory extinction is observed with lesions of the auditory cortex and auditory neglect. A distinction can nevertheless be made with dichotic target-detection tasks, auditory-lateralization perception, and magnetoencephalography. Copyright © 2012 Elsevier Ltd. All rights reserved.
Perception and action are coupled via bidirectional relationships between sensory and motor systems. Motor systems influence sensory areas by imparting a feedforward influence on sensory processing termed "motor efference copy" (MEC). MEC is suggested to occur in humans because speech preparation and production modulate neural measures of auditory cortical activity. However, it is not known if MEC can affect auditory perception. We tested the hypothesis that during speech preparation auditory thresholds will increase relative to a control condition, and that the increase would be most evident for frequencies that match the upcoming vocal response. Participants performed trials in a speech condition that contained a visual cue indicating a vocal response to prepare (one of two frequencies), followed by a go signal to speak. To determine threshold shifts, voice-matched or -mismatched pure tones were presented at one of three time points between the cue and target. The control condition was the same except the visual cues did not specify a response and subjects did not speak. For each participant, we measured f0 thresholds in isolation from the task in order to establish baselines. Results indicated that auditory thresholds were highest during speech preparation, relative to baselines and a non-speech control condition, especially at suprathreshold levels. Thresholds for tones that matched the frequency of planned responses gradually increased over time, but sharply declined for the mismatched tones shortly before targets. Findings support the hypothesis that MEC influences auditory perception by modulating thresholds during speech preparation, with some specificity relative to the planned response. The threshold increase in tasks vs. baseline may reflect attentional demands of the tasks.
Oscar E Ruiz
Full Text Available The cellular and molecular cues involved in creating branched tubular networks that transport liquids or gases throughout an organism are not well understood. To identify factors required in branching and lumen formation of Drosophila tracheal terminal cells, a model for branched tubular networks, we performed a forward genetic-mosaic screen to isolate mutations affecting these processes. From this screen, we have identified the first Drosophila mutation in the gene Zpr1 (Zinc finger protein 1 by the inability of Zpr1-mutant terminal cells to form functional, gas-filled lumens. We show that Zpr1 defective cells initiate lumen formation, but are blocked from completing the maturation required for gas filling. Zpr1 is an evolutionarily conserved protein first identified in mammalian cells as a factor that binds the intracellular domain of the unactivated epidermal growth factor receptor (EGFR. We show that down-regulation of EGFR in terminal cells phenocopies Zpr1 mutations and that Zpr1 is epistatic to ectopic lumen formation driven by EGFR overexpression. However, while Zpr1 mutants are fully penetrant, defects observed when reducing EGFR activity are only partially penetrant. These results suggest that a distinct pathway operating in parallel to the EGFR pathway contributes to lumen formation, and this pathway is also dependent on Zpr1. We provide evidence that this alternative pathway may involve fibroblast growth factor receptor (FGFR signaling.