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  • 1
    Online Resource
    Online Resource
    Society for Neuroscience ; 2010
    In:  The Journal of Neuroscience Vol. 30, No. 38 ( 2010-09-22), p. 12777-12786
    In: The Journal of Neuroscience, Society for Neuroscience, Vol. 30, No. 38 ( 2010-09-22), p. 12777-12786
    Abstract: Mutations in cyclin-dependent kinase-like 5 ( CDKL5 ), also known as serine/threonine kinase 9 ( STK9 ), have been identified in patients with Rett syndrome (RTT) and X-linked infantile spasm. However, the function of CDKL5 in the brain remains unknown. Here, we report that CDKL5 is a critical regulator of neuronal morphogenesis. We identified a neuron-specific splicing variant of CDKL5 whose expression was markedly induced during postnatal development of the rat brain. Downregulating CDKL5 by RNA interference (RNAi) in cultured cortical neurons inhibited neurite growth and dendritic arborization, whereas overexpressing CDKL5 had opposite effects. Furthermore, knocking down CDKL5 in the rat brain by in utero electroporation resulted in delayed neuronal migration, and severely impaired dendritic arborization. In contrast to its proposed function in the nucleus, we found that CDKL5 regulated dendrite development through a cytoplasmic mechanism. In fibroblasts and in neurons, CDKL5 colocalized and formed a protein complex with Rac1, a critical regulator of actin remodeling and neuronal morphogenesis. Overexpression of Rac1 prevented the inhibition of dendrite growth caused by CDKL5 knockdown, and the growth-promoting effect of ectopically expressed CDKL5 on dendrites was abolished by coexpressing a dominant-negative form of Rac1. Moreover, CDKL5 was required for brain-derived neurotrophic factor (BDNF)-induced activation of Rac1. Together, these results demonstrate a critical role of CDKL5 in neuronal morphogenesis and identify a Rho GTPase signaling pathway which may contribute to CDKL5-related disorders.
    Type of Medium: Online Resource
    ISSN: 0270-6474 , 1529-2401
    Language: English
    Publisher: Society for Neuroscience
    Publication Date: 2010
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  • 2
    Online Resource
    Online Resource
    Proceedings of the National Academy of Sciences ; 2023
    In:  Proceedings of the National Academy of Sciences Vol. 120, No. 8 ( 2023-02-21)
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 120, No. 8 ( 2023-02-21)
    Abstract: Microchromosomes are prevalent in nonmammalian vertebrates [P. D. Waters et al. , Proc. Natl. Acad. Sci. U.S.A. 118 (2021)], but a few of them are missing in bird genome assemblies. Here, we present a new chicken reference genome containing all autosomes, a Z and a W chromosome, with all gaps closed except for the W. We identified ten small microchromosomes (termed dot chromosomes) with distinct sequence and epigenetic features, among which six were newly assembled. Those dot chromosomes exhibit extremely high GC content and a high level of DNA methylation and are enriched for housekeeping genes. The pericentromeric heterochromatin of dot chromosomes is disproportionately large and continues to expand with the proliferation of satellite DNA and testis-expressed genes. Our analyses revealed that the 41-bp CNM repeat frequently forms higher-order repeats (HORs) at the centromeres of acrocentric chromosomes. The centromere core regions where the kinetochore attaches often encompass telomeric sequence (TTAGGG)n, and in a one of the dot chromosomes, the centromere core recruits an endogenous retrovirus (ERV). We further demonstrate that the W chromosome shares some common features with dot chromosomes, having large arrays of hypermethylated tandem repeats. Finally, using the complete chicken chromosome models, we reconstructed a fine picture of chordate karyotype evolution, revealing frequent chromosomal fusions before and after vertebrate whole-genome duplications. Our sequence and epigenetic characterization of chicken chromosomes shed insights into the understanding of vertebrate genome evolution and chromosome biology.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2023
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  • 3
    Online Resource
    Online Resource
    American Speech Language Hearing Association ; 2019
    In:  Journal of Speech, Language, and Hearing Research Vol. 62, No. 5 ( 2019-05-21), p. 1561-1573
    In: Journal of Speech, Language, and Hearing Research, American Speech Language Hearing Association, Vol. 62, No. 5 ( 2019-05-21), p. 1561-1573
    Abstract: A group of 10 prelingually deafened children with cochlear implants (CIs) formed a choir and received 21 months of formal music training. The purpose of this study was to evaluate the singing proficiency of these children. Method The participants included all choir members (7 girls and 3 boys, mean age of 9.5 years old) who were unilateral CI users. Meanwhile, 8 age-matched children with normal hearing were recruited as controls and were trained on 1 song for 2 weeks. Individual singing samples without instrument accompaniment were recorded from all participants. The singing samples were subject to acoustic analysis in which the fundamental frequency (F0) of each note was extracted and the duration was measured. Five metrics were developed and computed to quantify the accuracy of their pitch and rhythm performance. The 5 metrics included (a) percent correct of F0 contour direction of adjacent notes, (b) mean deviation of the normalized F0 across the notes, (c) mean deviation of the pitch intervals, (d) mean deviation of adjacent note duration ratio, and (e) mean absolute deviation of note duration. Results The choir members with CIs demonstrated high accuracy in both pitch and tempo measures and performed on par with the children with normal hearing. Early start of music training after implantation and use of bimodal hearing contributed to the development of better music ability in these children with CIs. Conclusion These findings indicated that rigorous music training could facilitate high singing proficiency in prelingually deafened children with CIs.
    Type of Medium: Online Resource
    ISSN: 1092-4388 , 1558-9102
    Language: English
    Publisher: American Speech Language Hearing Association
    Publication Date: 2019
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  • 4
    Online Resource
    Online Resource
    American Speech Language Hearing Association ; 2023
    In:  Journal of Speech, Language, and Hearing Research Vol. 66, No. 6 ( 2023-06-20), p. 2155-2176
    In: Journal of Speech, Language, and Hearing Research, American Speech Language Hearing Association, Vol. 66, No. 6 ( 2023-06-20), p. 2155-2176
    Abstract: This study assessed the intelligibility of obstruent consonants in prelingually deafened Mandarin-speaking children with cochlear implants (CIs). Method: Twenty-two Mandarin-speaking children with normal hearing (NH) aged 3.25–10.0 years and 35 Mandarin-speaking children with CIs aged 3.77–15.0 years were recruited to produce a list of Mandarin words composed of 17 word-initial obstruent consonants in different vowel contexts. The children with CIs were assigned to chronological age–matched (CA) and hearing age–matched (HA) subgroups with reference to the NH controls. One hundred naïve NH adult listeners were recruited for a consonant identification task that consisted of a total of 2,663 stimulus tokens through an online research platform. For each child speaker, the consonant productions were judged by seven to 12 different adult listeners. An average percentage of consonants correct was calculated across all listeners for each consonant. Results: The CI children in both the CA and HA subgroups showed lower intelligibility in their consonant productions than the NH controls. Among the 17 obstruents, both CI subgroups showed higher intelligibility for stops, but they demonstrated major problems with the sibilant fricatives and affricates and showed a different confusion pattern from the NH controls on these sibilants. Of the three places (alveolar, alveolopalatal, and retroflex) in Mandarin sibilants, both CI subgroups showed the lowest intelligibility and the greatest difficulties with alveolar sounds. For the NH children, there was a significant positive relationship between overall consonant intelligibility and chronological age. For the children with CIs, the best fit regression model revealed significant effects of chronological age and age at implantation, with their quadratic terms included. Conclusions: Mandarin-speaking children with CIs experience major challenges in the three-way place contrasts of sibilant sounds in consonant production. Chronological age and the combined effect of CI-related time variables play important roles in the development of obstruent consonants in the CI children.
    Type of Medium: Online Resource
    ISSN: 1092-4388 , 1558-9102
    Language: English
    Publisher: American Speech Language Hearing Association
    Publication Date: 2023
    detail.hit.zdb_id: 2070420-3
    SSG: 5,2
    SSG: 7,11
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  • 5
    Online Resource
    Online Resource
    Elsevier BV ; 2022
    In:  Speech Communication Vol. 136 ( 2022-01), p. 63-75
    In: Speech Communication, Elsevier BV, Vol. 136 ( 2022-01), p. 63-75
    Type of Medium: Online Resource
    ISSN: 0167-6393
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
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    detail.hit.zdb_id: 1460279-9
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  • 6
    Online Resource
    Online Resource
    Acoustical Society of America (ASA) ; 2016
    In:  Journal of the Acoustical Society of America Vol. 140, No. 4_Supplement ( 2016-10-01), p. 3445-3445
    In: Journal of the Acoustical Society of America, Acoustical Society of America (ASA), Vol. 140, No. 4_Supplement ( 2016-10-01), p. 3445-3445
    Abstract: The present study examined the dynamic features of compound vowels in native Mandarin-speaking children with cochlear implants (CIs). Fourteen prelingually deafened children with CIs (aged 2.9−8.3 years) and 14 age-matched, normal-hearing (NH) children produced monosyllables containing six Mandarin vowels (/aɪ/, /aʊ/, /uo/, /iɛ/, /iaʊ/, /ioʊ/). The frequency values of the first two formants were measured at nine equidistant time points (10-20-30-40-50-60-70-80-90%) over the course of vowel duration. All formant frequency values were normalized and then used to calculate vowel trajectory length, vowel section length, overall spectral rate of change, and vowel section rate of change. The results revealed that the CI children produced significantly longer durations for all six compound vowels. They clearly showed positional deviation from the NH children on vowels /aɪ/, /uo/ and /iɛ/. The CI children’s ability to produce formant movement for the compound vowels varied considerably. Some CI children produced relatively static formant trajectories for certain diphthongs whereas others produced certain vowels with greater formant movement than did the NH children. As a group, the CI children roughly followed the NH children on patterns of vowel dynamic spectral change, but they moved the articulators with a slower rate of change than did the NH children.
    Type of Medium: Online Resource
    ISSN: 0001-4966 , 1520-8524
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    Language: English
    Publisher: Acoustical Society of America (ASA)
    Publication Date: 2016
    detail.hit.zdb_id: 1461063-2
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  • 7
    Online Resource
    Online Resource
    Acoustical Society of America (ASA) ; 2022
    In:  The Journal of the Acoustical Society of America Vol. 151, No. 4_Supplement ( 2022-04-01), p. A65-A65
    In: The Journal of the Acoustical Society of America, Acoustical Society of America (ASA), Vol. 151, No. 4_Supplement ( 2022-04-01), p. A65-A65
    Abstract: The purpose of this study was to assess the accuracy of consonant production of children with cochlear implants (CIs) judged by naïve adult listeners. A total of 57 Mandarin-speaking children (22 with normal hearing and 35 with CIs) were recruited to produce a list of Mandarin words composed of 17 word-initial obstruent consonants in three different vowel contexts. A total number of 2628 tokens were generated and were divided into 10 subsets. One hundred Mandarin-speaking naïve adult listeners were recruited to identify the consonant productions through Gorilla, the online research platform. Each listener was randomly assigned to one subset. For each child speaker, the consonant productions were judged by 7–12 adult listeners and an average accuracy rate was calculated across all listeners for each consonant. The results revealed that the children with CIs showed lower accuracies and different confusion patterns on their consonant productions than the normal hearing controls. In particular, they demonstrated higher accuracy for stops but had major problems with the fricatives and affricates involved in the alveolar—alveolopalatal—retroflex postalveolar three-way sibilant contrast. Of the three places of the sibilant contrast, they showed the greatest difficulties for the alveolar sounds.
    Type of Medium: Online Resource
    ISSN: 0001-4966 , 1520-8524
    RVK:
    Language: English
    Publisher: Acoustical Society of America (ASA)
    Publication Date: 2022
    detail.hit.zdb_id: 1461063-2
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  • 8
    Online Resource
    Online Resource
    Acoustical Society of America (ASA) ; 2012
    In:  The Journal of the Acoustical Society of America Vol. 131, No. 4_Supplement ( 2012-04-01), p. 3479-3479
    In: The Journal of the Acoustical Society of America, Acoustical Society of America (ASA), Vol. 131, No. 4_Supplement ( 2012-04-01), p. 3479-3479
    Abstract: This series of studies was aimed to investigate how listeners with sensorineural hearing loss (SNHL) and with auditory neuropathy syndrome disorder (ANSD) achieved lexical tone recognition using either the temporal envelope (E) or the fine structure (FS) cues. Five groups of Mandarin-speaking subjects, including (1) 22 normal-hearing subjects, (2) 8 moderate, (3) 13 moderate to severe, (4) 10 severe SNHL patients with various degrees of SNHL, and (5) 10 patients with ANSD, participated in the study. Monosyllabic words were processed through a 16-channel “auditory chimera” in which E from a monosyllabic word of one tone was paired with FS from the same monosyllable of other tones. On average, 92.0%, 67.4%, 58.1%, 37.5%, and 17.1% of the tone responses were consistent with FS cues, while 5.8%, 23.7%, 31.1%, 45.2%, 42.7% of the tone responses were consistent with E cues for the 5 groups of subjects mentioned above. Therefore, as the hearing loss becomes more severe, the ability of SNHL patients to use FS for tone recognition becomes more deteriorated. The ability of ANSD subjects to use FS is even poorer than patients with severe SNHL even though their pure-tone thresholds were only moderately elevated in the low and mid frequencies.
    Type of Medium: Online Resource
    ISSN: 0001-4966 , 1520-8524
    RVK:
    Language: English
    Publisher: Acoustical Society of America (ASA)
    Publication Date: 2012
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  • 9
    Online Resource
    Online Resource
    Acoustical Society of America (ASA) ; 2018
    In:  The Journal of the Acoustical Society of America Vol. 144, No. 3_Supplement ( 2018-09-01), p. 1863-1863
    In: The Journal of the Acoustical Society of America, Acoustical Society of America (ASA), Vol. 144, No. 3_Supplement ( 2018-09-01), p. 1863-1863
    Abstract: The present study examined the joint influence of listeners’ language experience and the degree of spectral degradation of speech signals on English phoneme recognition of L2 listeners. The participants included 27 native English-speaking listeners and 43 native Mandarin-speaking listeners who used English as an L2. The L2 participants varied in chronological age, age of English learning, length of residency in the United States, and the amount of daily-based English usage. The speech stimuli included 12 English vowels embedded in a /hVd/ context produced by four speakers and 20 English consonants embedded in a /Ca/ context produced by two speakers. The speech stimuli were processed using 2-, 4-, 6-, 8-, and 12-channel noise vocoders. The processed and original stimuli were presented to the listeners for identification in a random order. The results showed that spectral degradation had more adverse effects on the L2 listeners but the L2 disadvantage became more evident as the number of frequency increased. The L2 listeners showed different confusion patterns from the L1 listeners, which was affected by the L2 listeners’ native language experience. Furthermore, the regression analysis revealed that the L2 listener’s length of residency in the United States was a significant predictor for their phoneme recognition outcomes.
    Type of Medium: Online Resource
    ISSN: 0001-4966 , 1520-8524
    RVK:
    Language: English
    Publisher: Acoustical Society of America (ASA)
    Publication Date: 2018
    detail.hit.zdb_id: 1461063-2
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  • 10
    Online Resource
    Online Resource
    Proceedings of the National Academy of Sciences ; 2013
    In:  Proceedings of the National Academy of Sciences Vol. 110, No. 47 ( 2013-11-19), p. 19131-19136
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 110, No. 47 ( 2013-11-19), p. 19131-19136
    Abstract: Opitz syndrome (OS) is a genetic neurological disorder. The gene responsible for the X-linked form of OS, Midline-1 ( MID1 ), encodes an E3 ubiquitin ligase that regulates the degradation of the catalytic subunit of protein phosphatase 2A (PP2Ac). However, how Mid1 functions during neural development is largely unknown. In this study, we provide data from in vitro and in vivo experiments suggesting that silencing Mid1 in developing neurons promotes axon growth and branch formation, resulting in a disruption of callosal axon projections in the contralateral cortex. In addition, a similar phenotype of axonal development was observed in the Mid1 knockout mouse. This defect was largely due to the accumulation of PP2Ac in Mid1-depleted cells as further down-regulation of PP2Ac rescued the axonal phenotype. Together, these data demonstrate that Mid1-dependent PP2Ac turnover is important for normal axonal development and that dysregulation of this process may contribute to the underlying cause of OS.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2013
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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