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1.

Background

Cullin ubiquitin ligases are activated via the covalent modification of Cullins by the small ubiquitin-like protein nedd8 in a process called neddylation. Genetic mutations of cullin-4b (cul4b) cause a prevalent type of X-linked intellectual disability (XLID) in males, but the physiological function of Cul4B in neuronal cells remains unclear.

Results

There are three major isoforms of Cul4B (1, 2, and 3) in human and rodent tissues. By examining the endogenous Cul4B isoforms in the brain, this study demonstrates that Cul4B-1 and Cul4B-2 isoforms are unneddylated and more abundant in the brain whereas the lesser species Cul4B-3 that misses the N-terminus present in the other two isoforms is neddylated. The data suggest that the N-terminus of Cul4B inhibits neddylation in the larger isoforms. Immunostaining of human NT-2 cells also shows that most Cul4B is unneddylated, especially when it is localized in the process in G0-synchronized cells. This study demonstrates that Cul4B accumulates during mitosis and downregulation of Cul4B arrests NPCs and NT-2 cells in the G2/M phase of the cell cycle. In both human and rodent brain tissues, Cul4B-positive cells accumulate ??-catenin in the dentate subgranular zone and the subventricular zone. These Cul4B-positive cells also co-express the MPM-2 mitotic epitope, suggesting that Cul4B is also necessary for mitosis progression in vivo.

Conclusions

This study provides first evidence that unneddylated Cul4B isoforms exist in the brain and are necessary for mitosis progression in NPCs. The data suggest that unneddylated Cul4B isoforms specifically inhibits ??-catenin degradation during mitosis. Furthermore, unneddylated Cul4B may play a role in addition to cell cycle since it is exclusively localized to the processes in starved NT-2 cells. Further analyses of the different isoforms of Cul4B will help understand the cognitive deficits in Cul4B-linked XLID and give insights into drug and biomarker discoveries.  相似文献   

2.
Cortical activation in visual association areas known to be responsible for the perception of motion was investigated in two volunteers who viewed a projected animated cartoon periodically “run” and “frozen” during collection of echoplanar MR images. Ten axial, contiguous, 5 mm thick, T2-weighted, gradient-echo images (TE 40 ms, TR 3000 ms) depicting BOLD contrast were acquired through the occipital lobe using a GE Signa 1.5 T system with an advanced NMR operating console. Images were analysed by time series regression modelling estimating power in the MR signal at the ON-OFF frequency of motion. Highly significant activation in response to motion perception was identified in both subjects bilaterally in area V5.  相似文献   

3.
A cine series of tagged magnetic resonance (MR) images of the tongue is used to measure tongue motion and its internal deformation during speech. Tagged images are collected in three slice orientations (sagittal, coronal, and axial) during repetitions of the utterance "disouk" (/disuk/). A new technique called harmonic phase MRI (HARP-MRI) is used to process the tagged MR images to measure the internal deformation of the tongue. The measurements include displacement and velocity of tissue points, principal strains, and strain in the line-of-action of specific muscles. These measurements are not restricted to tag intersections, but can be calculated at every pixel in the image. The different motion measurements complement each other in understanding the tongue kinematics and in hypothesizing the internal muscle activity of the tongue.  相似文献   

4.
Prior to the development of Special Relativity, no restrictions were imposed on the velocity of the motion of particles and material bodies, as well as on energy transfer and signal propagation. At the end of the 19th century and the beginning of the 20th century, it was shown that a charge that moves at a velocity faster than the speed of light in an optical medium, in particular, in vacuum, gives rise to impact radiation, which later was termed the Vavilov-Cherenkov radiation. Shortly after the development of Special Relativity, some researchers considered the possibility of superluminal motion. In 1923, the Soviet physicist L.Ya. Strum suggested the existence of tachyons, which, however, have not been discovered yet. Superluminal motions can occur only for images, e.g., for so-called ??light spots,?? which were considered in 1972 by V.L. Ginzburg and B.M. Bolotovskii. These spots can move with a superluminal phase velocity but are incapable of transferring energy and information. Nevertheless, these light spots may induce quite real generation of microwave radiation in closed waveguides and create the Vavilov-Cherenkov radiation in vacuum. In this work, we consider various paradoxes, illusions, and artifacts associated with superluminal motion.  相似文献   

5.
Subjects presented with coherent auditory and visual streams generally fuse them into a single percept. This results in enhanced intelligibility in noise, or in visual modification of the auditory percept in the McGurk effect. It is classically considered that processing is done independently in the auditory and visual systems before interaction occurs at a certain representational stage, resulting in an integrated percept. However, some behavioral and neurophysiological data suggest the existence of a two-stage process. A first stage would involve binding together the appropriate pieces of audio and video information before fusion per se in a second stage. Then it should be possible to design experiments leading to unbinding. It is shown here that if a given McGurk stimulus is preceded by an incoherent audiovisual context, the amount of McGurk effect is largely reduced. Various kinds of incoherent contexts (acoustic syllables dubbed on video sentences or phonetic or temporal modifications of the acoustic content of a regular sequence of audiovisual syllables) can significantly reduce the McGurk effect even when they are short (less than 4?s). The data are interpreted in the framework of a two-stage "binding and fusion" model for audiovisual speech perception.  相似文献   

6.
Understanding the segmental dynamics of polymer chains is cardinal to decipher the microscopic behaviour in order to modulate the bulk properties of polymers. The study of electron spin resonance (ESR) spectroscopy of spin-labelled polymers is useful to understand the segmental dynamics of polymer chains in solution. In this paper, poly(acrylic acid)s (PAAs) were spin labelled with 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl radicals. Spin-labelled PAAs (SL-PAAs) were characterised by Fourier-transform infrared spectroscopy, ultraviolet–visible spectroscopy, thermogravimetric analysis, differential scanning calorimetry, cyclic voltammetry (CV), and ESR analyses. The polyelectrolyte complexes of SL-PAAs were prepared by employing poly(diallyldimethylammonium chloride) (PDADMAC) as the polycation and analysed by transmission electron microscopy, dynamic light scattering (DLS), and ESR spectroscopies. The effect of molar mass on the segmental dynamics of SL-PAAs in pristine as well as in the form of polyelectrolyte complexes (PECs) was studied. The results indicated that SL-PAAs show a differential complexation behaviour with PDADMAC in the PECs depending on their molar mass.  相似文献   

7.
Two experiments were conducted to explore the effectiveness of a single vibrotactile stimulator to convey intonation (question versus statement) and contrastive stress (on one of the first three words of four 4- or 5-word sentences). In experiment I, artificially deafened normal-hearing subjects judged stress and intonation in counterbalanced visual-alone and visual-tactile conditions. Six voice fundamental frequency-to-tactile transformations were tested. Two sentence types were voiced throughout, and two contained unvoiced consonants. Benefits to speechreading were significant, but small. No differences among transformations were observed. In experiment II, only the tactile stimuli were presented. Significant differences emerged among the transformations, with larger differences for intonation than for stress judgments. Surprisingly, tactile-alone intonation identification was more accurate than visual-tactile for several transformations.  相似文献   

8.
Several diffusion processes have been observed in ceramic β-eucryptite using NMR methods. One low activation energy (0.25 eV) process has been identified with the high temperature disordered phase of the lattice. NMR deduced jump rates agree well with Raman scattering experiments.  相似文献   

9.
There is information in speech sounds about the length of the vocal tract; specifically, as a child grows, the resonators in the vocal tract grow and the formant frequencies of the vowels decrease. It has been hypothesized that the auditory system applies a scale transform to all sounds to segregate size information from resonator shape information, and thereby enhance both size perception and speech recognition [Irino and Patterson, Speech Commun. 36, 181-203 (2002)]. This paper describes size discrimination experiments and vowel recognition experiments designed to provide evidence for an auditory scaling mechanism. Vowels were scaled to represent people with vocal tracts much longer and shorter than normal, and with pitches much higher and lower than normal. The results of the discrimination experiments show that listeners can make fine judgments about the relative size of speakers, and they can do so for vowels scaled well beyond the normal range. Similarly, the recognition experiments show good performance for vowels in the normal range, and for vowels scaled well beyond the normal range of experience. Together, the experiments support the hypothesis that the auditory system automatically normalizes for the size information in communication sounds.  相似文献   

10.
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 discrimination with pure tones and broadband noise, tone-in-noise detection, spectral masking with narrow-band signals and maskers, forward masking with tone signals and tone or noise maskers, and amplitude-modulation detection with narrow- and wideband noise carriers. The model can account for most of the key properties of the data and is more powerful than the original model. The model might be useful as a front end in technical applications.  相似文献   

11.
A single pool of untrained subjects was tested for interactions across two bimodal perception conditions: audio-tactile, in which subjects heard and felt speech, and visual-tactile, in which subjects saw and felt speech. Identifications of English obstruent consonants were compared in bimodal and no-tactile baseline conditions. Results indicate that tactile information enhances speech perception by about 10 percent, regardless of which other mode (auditory or visual) is active. However, within-subject analysis indicates that individual subjects who benefit more from tactile information in one cross-modal condition tend to benefit less from tactile information in the other.  相似文献   

12.
13.
《Nuclear Physics A》1987,465(3):379-396
A new method is proposed to derive a collective boson Hamilton operator in an equation of motion approach starting from a microscopic shell-model hamiltonian with effective residual interactions. The method is used to describe pairing vibrations in spherical open shell nuclei in terms of interacting bosons. The results are in fair agreement with experimental data.  相似文献   

14.
《Nuclear Physics A》1987,467(3):422-436
Based on the shell structure of the finite nuclear many fermion system (FMFS), the coherent states related to the Spin(2r) group are defined. The global and local functional representations of the FMFS state-vectors and operators, defined on the coset space Spin(2r)/U(r), are constructed. The nonuniqueness of the coherent state functional representations is overcome by the imposition of a consistency condition on the wave functions. The influence of the boundary of the coset space Spin(2r)/U(r) on the local functional representation is physically removed only for the bound states of FMFS. The reason for the non-hermitian behavior of the local functional representation is exposed. Finally, using Bargmann's theory, the boson representation of FMFS are directly calculated from the local functional representation of FMFS. Thus, in this paper, we have demonstrated that the kinematics of the collective behavior of FMFS can be described in three non-equivalent representations: the fermion representation, the global functional representation and the local functional representation.  相似文献   

15.
In Part I [Purwins H, Herrera P, Grachten M, Hazan A, Marxer R, Serra X. Computational models of music perception and cognition I: The perceptual and cognitive processing chain. Physics of Life Reviews 2008, in press, doi:10.1016/j.plrev.2008.03.004], we addressed the study of cognitive processes that underlie auditory perception of music, and their neural correlates. The aim of the present paper is to summarize empirical findings from music cognition research that are relevant to three prominent music theoretic domains: rhythm, melody, and tonality. Attention is paid to how cognitive processes like category formation, stimulus grouping, and expectation can account for the music theoretic key concepts in these domains, such as beat, meter, voice, consonance. We give an overview of computational models that have been proposed in the literature for a variety of music processing tasks related to rhythm, melody, and tonality. Although the present state-of-the-art in computational modeling of music cognition definitely provides valuable resources for testing specific hypotheses and theories, we observe the need for models that integrate the various aspects of music perception and cognition into a single framework. Such models should be able to account for aspects that until now have only rarely been addressed in computational models of music cognition, like the active nature of perception and the development of cognitive capacities from infancy to adulthood.  相似文献   

16.
This study considered consequences of sensorineural hearing loss in ten listeners. The characterization of individual hearing loss was based on psychoacoustic data addressing audiometric pure-tone sensitivity, cochlear compression, frequency selectivity, temporal resolution, and intensity discrimination. In the experiments it was found that listeners with comparable audiograms can show very different results in the supra-threshold measures. In an attempt to account for the observed individual data, a model of auditory signal processing and perception [Jepsen et al., J. Acoust. Soc. Am. 124, 422-438 (2008)] was used as a framework. The parameters of the cochlear processing stage of the model were adjusted to account for behaviorally estimated individual basilar-membrane input-output functions and the audiogram, from which the amounts of inner hair-cell and outer hair-cell losses were estimated as a function of frequency. All other model parameters were left unchanged. The predictions showed a reasonably good agreement with the measured individual data in the frequency selectivity and forward masking conditions while the variation of intensity discrimination thresholds across listeners was underestimated by the model. The model and the associated parameters for individual hearing-impaired listeners might be useful for investigating effects of individual hearing impairment in more complex conditions, such as speech intelligibility in noise.  相似文献   

17.
Summary Both bottom-up sensory information and top-down influences contribute to the perception processes. We studied the perceptual alternations of a multistable ambiguous pattern. We observed that it is possible to interfere on the process of the perception alternance by means of subliminal visual stimuli, which either contrast or second the previous perception. We investigated also the effect of the top-down volitional factor on the perceptual alternation. By using a combination of such top-down factor and bottom-up stimulation, we ascertained that a non-linear type of interaction occurs between the two above factors. Paper presented at the International Workshop ?Fluctuations in Physics and Biology: Stochastic Resonance, Signal Processing and Related Phenomena?, Elba, 5–10 June 1994.  相似文献   

18.
The smoothing efficiencies of epicyclic motion and orbital motion in CCOS (computer controlled optical surfacing) were compared. CCOS polishing can smooth out mid-to-high spatial frequency errors which are smaller than tool size on optical mirrors due to the rigidity of polishing tools. The smoothing efficiencies of epicyclic motion and orbital motion with pitch lap and RC lap were compared and the result proved pitch lap with epicyclic motion smoothed ∼1.6 times faster than pitch lap with orbital motion while RC lap with epicyclic motion smoothed ∼1.85 times faster than RC lap with orbital motion.  相似文献   

19.
20.
We show that, under suitable confinement conditions, the ordinary Fokker-Planck equation may generate non-Gaussian heavy-tailed probability density functions (pdfs) (like, for example, Cauchy or more general Lévy stable distributions) in its long-time asymptotics. In fact, all heavy-tailed pdfs known in the literature can be obtained this way. For the underlying diffusion-type processes, our main focus is on their transient regimes and specifically the crossover features, when an initially infinite number of pdf moments decreases to a few or none at all. The time dependence of the variance (if in existence), ∼tγ with 0<γ<2, may in principle be interpreted as a signature of subdiffusive, normal diffusive or superdiffusive behavior under confining conditions; the exponent γ is generically well defined in substantial periods of time. However, there is no indication of any universal time rate hierarchy, due to a proper choice of the driver and/or external potential.  相似文献   

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