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The present study examined the cross-modal cueing effect of musical rhythmic beats on non-native speech rhythm production. Two groups of Chinese learners of French were cued respectively with rhythmic beats that either matched (matching group) or mismatched (mismatching group) the rhythm patterns of the target French sentences. The participants were asked to produce the target sentences after cueing and their speech production was compared with their baseline condition in which no cueing was used. The results showed that the matching group produced the target French rhythm significantly better after cueing with musical rhythmic beats that matched the French rhythm, in contrast to the mismatching group where no significant improvement was found. Individual differences in auditory short-term memory and rhythmic skills were not related to improvement in producing French rhythm after cueing. The results suggest that musical rhythmic cueing can be used to improve non-native speech rhythm production, further indicating a close link between speech and music in the temporal domain.
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Música , Percepción del Habla , Humanos , Habla , Lenguaje , ChinaRESUMEN
How could individual differences in processing non-speech acoustic signals influence their cue weighting strategies for L2 speech contrasts? The present study investigated this question by testing forty L1 Chinese-L2 English listeners with two tasks: one for testing the listeners' sensitivity to pitch and temporal information of non-speech acoustic signals; the other for testing their cue weighting (VOT, F0) strategies for distinguishing voicing contrasts in English stop consonants. The results showed that the more sensitive the listeners were to temporal differences of non-speech acoustic signals, the more they relied on VOT to differentiate between the voicing contrasts in English stop consonants. No such association was found between listeners' differences in sensitivity to pitch changes of non-speech acoustic signals and their reliance on F0 to cue the voicing contrasts. The results could shed light on the different processing mechanisms for pitch and temporal information of acoustic signals.
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Acústica del Lenguaje , Percepción del Habla , Acústica , Señales (Psicología) , Humanos , Individualidad , FonéticaRESUMEN
Speech and music reflect extraordinary aspects of human cognitive abilities. Pitch, as an important parameter in the auditory domain, has been the focus of previous research on the relations between speech and music. The present study continues this line of research by focusing on two aspects of pitch processing: pitch prominence and melodic expectation. Specifically, we examined the perceived boundary of prominence for focus/accent in speech and music, plus the comparison between the pitch expectation patterns of music and speech. Speech (Mandarin Chinese) and music stimuli were created with different interval steps that increased from 1 semitone to 12 semitones from the third to the fourth word/note of a sentence/melody. The results showed that ratings of both accent/focus and expectation/surprise increased with increasing semitone distance from the baseline (though this pattern was mixed with tonal stability profiles for the melodies). Nevertheless, the perceived boundary of prominence was different for music and speech, with the boundary for detecting prominence in speech higher than that in music. Expectation also showed different patterns for speech and music. The results thus favor the suggestion that speech prosody and music melody tend to require specialized pitch patterns unique to their own respective communication purposes.
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F0 variation is a crucial feature in speech prosody, which can convey linguistic information such as focus and paralinguistic meanings such as surprise. How can multiple layers of information be represented with F0 in speech: are they divided into discrete layers of pitch or overlapped without clear divisions? We investigated this question by assessing pitch perception of focus and surprise in Mandarin Chinese. Seventeen native Mandarin listeners rated the strength of focus and surprise conveyed by the same set of synthetically manipulated sentences. An fMRI experiment was conducted to assess neural correlates of the listeners' perceptual response to the stimuli. The results showed that behaviourally, the perceptual threshold for focus was 3 semitones and that for surprise was 5 semitones above the baseline. Moreover, the pitch range of 5-12 semitones above the baseline signalled both focus and surprise, suggesting a considerable overlap between the two types of prosodic information within this range. The neuroimaging data positively correlated with the variations in behavioural data. Also, a ceiling effect was found as no significant behavioural differences or neural activities were shown after reaching a certain pitch level for the perception of focus and surprise respectively. Together, the results suggest that different layers of prosodic information are represented in F0 through different pitch ranges: paralinguistic information is represented at a pitch range beyond that used by linguistic information. Meanwhile, the representation of paralinguistic information is achieved without obscuring linguistic prosody, thus allowing F0 to represent the two layers of information in parallel.
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Percepción del Habla , China , Humanos , Lenguaje , Percepción de la Altura Tonal , HablaRESUMEN
Previous studies in speech production and acquisition have mainly focused on how feedback vs. goals and feedback vs. prediction regulate learning and speech control. The present study investigated the less studied mechanism-prediction vs. goals in the context of adult Mandarin speakers' acquisition of non-native sounds, using an auditory feedback masking paradigm. Participants were asked to learn two types of non-native vowels: /ø/ and /ɵ/-the former being less similar than the latter to Mandarin vowels, either in feedback available or feedback masked conditions. The results show that there was no significant improvement in learning the two targets when auditory feedback was masked. This suggests that motor-based prediction could not directly compare with sensory goals for adult second language acquisition. Furthermore, auditory feedback can help achieve learning only if the competition between prediction and goals is minimal, i.e., when target sounds are distinct from existing sounds in one's native speech. The results suggest motor-based prediction and sensory goals may share a similar neural representational format, which could result in a competing relation in neural recourses in speech learning. The feedback can conditionally overcome such interference between prediction and goals. Hence, the present study further probed the functional relations among key components (prediction, goals and feedback) of sensorimotor integration in speech learning.
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Retroalimentación Sensorial/fisiología , Lenguaje , Aprendizaje/fisiología , Fonética , Acústica del Lenguaje , Percepción del Habla/fisiología , Estimulación Acústica , Adulto , China , Femenino , Humanos , Masculino , Enmascaramiento Perceptual/fisiología , Habla/fisiologíaRESUMEN
Music and speech both communicate emotional meanings in addition to their domain-specific contents. But it is not clear whether and how the two kinds of emotional meanings are linked. The present study is focused on exploring the emotional connotations of musical timbre of isolated instrument sounds through the perspective of emotional speech prosody. The stimuli were isolated instrument sounds and emotional speech prosody categorized by listeners into anger, happiness and sadness, respectively. We first analyzed the timbral features of the stimuli, which showed that relations between the three emotions were relatively consistent in those features for speech and music. The results further echo the size-code hypothesis in which different sound timbre indicates different body size projections. Then we conducted an ERP experiment using a priming paradigm with isolated instrument sounds as primes and emotional speech prosody as targets. The results showed that emotionally incongruent instrument-speech pairs triggered a larger N400 response than emotionally congruent pairs. Taken together, this is the first study to provide evidence that the timbre of simple and isolated musical instrument sounds can convey emotion in a way similar to emotional speech prosody.
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BACKGROUND: Mesangial cell (MC) proliferation and apoptosis are the main pathological changes observed in mesangial proliferative nephritis. In this study, we explored the role of cyclins and p53 in modulating MC proliferation and apoptosis in a mouse model of Habu nephritis. METHODS: The Habu nephritis group was prepared by injection of Habu toxin. Mesangiolysis and mesangial expansion were determined by periodic acid-Schiff (PAS) reagent staining. Immunohistochemical analysis of PCNA and KI67, and TUNEL staining were used to detect cell proliferation and apoptosis, respectively. Expression levels of cyclins and p53 were examined by Western blotting. RESULTS: PAS staining showed that mesangial dissolution appeared on days 1 and 3, and mesangial proliferation with extracellular matrix accumulation was apparent by days 7 and 14. Both PCNA and KI67 immunohistochemical analysis showed that MC proliferation began on day 3, peaked on day 3 and 7, and recovered by day 14. TUNEL staining results showed that MC apoptosis began to increase on day 1, continued to rise on day 7, and peaked on day 14. Western blot analysis showed that cyclin D1 was upregulated on day 1, cyclins A2 and E were upregulated on days 3 and 7, and p53 was upregulated on days 3, 7 and 14. There was no change in the expression levels of Bax or p21. CONCLUSION: We explored the tendency for MC proliferation and apoptosis during the process of Habu nephritis and found that cyclins and p53 may modulate the disease pathology. This will help us determine the molecular pathogenesis of MC proliferation and provide new targets for disease intervention.
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Ciclinas/metabolismo , Glomerulonefritis/etiología , Células Mesangiales/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Animales , Apoptosis , Venenos de Crotálidos , Modelos Animales de Enfermedad , Glomerulonefritis/metabolismo , Glomerulonefritis/patología , Masculino , Células Mesangiales/patología , Ratones Endogámicos C57BL , Transducción de SeñalRESUMEN
This study compares affective piano performance with speech production from the perspective of dynamics: unlike previous research, this study uses finger force and articulatory effort as indexes reflecting the dynamics of affective piano performance and speech production respectively. Moreover, for the first time physical constraints such as piano fingerings and speech articulatory constraints are included due to their potential contribution to different patterns of dynamics. A piano performance experiment and speech production experiment were conducted in four emotions: anger, fear, happiness and sadness. The results show that in both piano performance and speech production, anger and happiness generally have high dynamics while sadness has the lowest dynamics. Fingerings interact with fear in the piano experiment and articulatory constraints interact with anger in the speech experiment, i.e., large physical constraints produce significantly higher dynamics than small physical constraints in piano performance under the condition of fear and in speech production under the condition of anger. Using production experiments, this study firstly supports previous perception studies on relations between affective music and speech. Moreover, this is the first study to show quantitative evidence for the importance of considering motor aspects such as dynamics in comparing music performance and speech production in which motor mechanisms play a crucial role.
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MAX interactor 1 (Mxi1) proteins are c-myc antagonists that primarily exert their biological functions by inhibiting Myc-dependent gene transcription. In this study, Mxi1(-/-) mice were used to generate a model of mesangial proliferative glomerulonephritis for the first time. In the present study, we demonstrated that Mxi1(-/-) mice exhibited a more typical and severe pathological phenotype, which was displayed primarily as a noticeable dissolution phenotype with a higher proportion of apoptotic cells and higher chemokine CXCL10 expression during the early days of modeling, compared with wild-type mice. Additionally, we determined that IRF3-mediated TLR4 signaling was likely involved in regulating CXCL10 expression, which might participate in the mesangial dissolution process. We also found increases in CXCL10 expression, caspase 3 activation, and the proportion of apoptotic cells when Mxi1 expression was inhibited in mouse mesangial cells. Furthermore, the proportion of apoptotic cells decreased after inhibiting CXCL10 expression. Therefore, we concluded that the mesangial cell apoptosis observed in this mesangial proliferative glomerulonephritis model was related to CXCL10 expression induced by Mxi1 inactivation. This finding provides a new theoretical basis for the mechanism of mesangial proliferative glomerulonephritis progression and reveals potential intervention targets for the early treatment of this disease.
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Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Quimiocina CXCL10/genética , Regulación de la Expresión Génica , Glomerulonefritis/genética , Glomerulonefritis/patología , Glomérulos Renales/patología , Células Mesangiales/patología , Proteínas Supresoras de Tumor/genética , Animales , Apoptosis , Caspasa 3/metabolismo , Venenos de Crotálidos , Eliminación de Gen , Glomerulonefritis/inducido químicamente , Glomerulonefritis/metabolismo , Glomérulos Renales/metabolismo , Masculino , Células Mesangiales/citología , Células Mesangiales/metabolismo , Ratones , Transducción de Señal , Receptor Toll-Like 4/metabolismo , Trimeresurus , Regulación hacia ArribaRESUMEN
The mechanism of mesenchymal stem cell therapy in acute kidney injury remains uncertain. Previous studies indicated that mesenchymal stem cells could attenuate inflammation-related organ injury by induction of regulatory T cells. Whether regulatory T-cell induction is a potential mechanism of mesenchymal stem cell therapy in ischemic acute kidney injury and how these induced regulatory T cells orchestrate local inflammation are unknown. Here we found that mesenchymal stem cells decrease serum creatinine and urea nitrogen levels, improve tubular injury, and downregulate IFN-γ production of T cells in the ischemic kidney. In addition to the lung, mesenchymal stem cells persisted mostly in the spleen. Mesenchymal stem cells increased the percentage of regulatory T cells in the spleen and the ischemic kidney. Antibody-dependent depletion of regulatory T cells blunted the therapeutic effect of mesenchymal stem cells, while coculture of splenocytes with mesenchymal stem cells caused an increase in the percentage of regulatory T cells. Splenectomy abrogated attenuation of ischemic injury, and downregulated IFN-γ production and the induction of regulatory T cells by mesenchymal stem cells. Thus, mesenchymal stem cells ameliorate ischemic acute kidney injury by inducing regulatory T cells through interactions with splenocytes. Accumulated regulatory T cells in ischemic kidney might be involved in the downregulation of IFN-γ production.
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Lesión Renal Aguda/patología , Lesión Renal Aguda/terapia , Comunicación Celular/fisiología , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/patología , Bazo/patología , Linfocitos T Reguladores/patología , Lesión Renal Aguda/fisiopatología , Animales , Nitrógeno de la Urea Sanguínea , Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Creatinina/sangre , Modelos Animales de Enfermedad , Interferón gamma/metabolismo , Riñón/patología , Ratones , Ratones Endogámicos C57BL , Bazo/cirugía , EsplenectomíaRESUMEN
BACKGROUND/AIMS: The Kruppel-like factor-15 (KLF15), a DNA-binding transcription factor, is highly expressed in endothelial and mesangial cells of the kidney. However, its effects on mesangial cell proliferation have not previously been investigated. In this study, we investigated the effect of KLF15 on mesangial cell proliferation. METHODS: We established a classic rat anti-Thy1 mesangial proliferative nephritis model. Affymetrix rat U230 2.0 chip was used to detect the gene expression profiles at different time point in the model. The different expression of KLF15 was shown during mesangial cell proliferation period and proliferation declined period of anti-Thy1 nephritis model by microarray analysis, Real-time PCR and Western blotting. Then we determined the effects of KLF15 and its downstream target, cell cycle regulation factor E2F1 on the proliferation of mesangial cells and the expression of the positive-acting cell cycle regulatory proteins, cyclinD1 and CDK2, by means of positive and negative interference experiments in cultured rat mesangial cells. We detected also protein expression of E2F1, cyclinD1 and CDK2 in vivo. RESULTS: By real-time PCR, Western blotting, and microarray analysis, KLF15 expression was shown to be lower during mesangial cell proliferation period and higher during proliferation declined period and under normal conditions. The mesangial cell proliferation was reduced and the expression of E2F1, cyclin D1 and CDK2 was downregulated in mesangial cells overexpressing KLF15. When KLF15 expression was inhibited by siRNA, the expression of E2F1, cyclin D1 and CDK2 and mesangial cell proliferation were increased. When E2F1 was inhibited by siRNA, protein level of CDK2 and cyclin D1 were lower than control. When siE2F1 was co-transfected with siKLF15 into mesangial cells, the increase of cell proliferation induced by siKLF15 was eliminated partly by siE2F1. Moreover, E2F1, cyclin D1 and CDK2 were higher expression during mesangial cell proliferation period, and were downregulated during proliferation declined period in vivo. CONCLUSIONS: These results suggest that KLF15 inhibits mesangial cell proliferation, possibly by regulating the expression of cell cycle regulation proteins through E2F1. Thus, KLF15 may be a useful target for therapeutic intervention in mesangial proliferative glomerulonephritis.
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Proliferación Celular , Mesangio Glomerular/citología , Factores de Transcripción de Tipo Kruppel/fisiología , Animales , Secuencia de Bases , Western Blotting , Proteínas de Ciclo Celular/metabolismo , Células Cultivadas , Cartilla de ADN , Citometría de Flujo , Inmunohistoquímica , Factores de Transcripción de Tipo Kruppel/genética , Masculino , ARN Mensajero/genética , ARN Interferente Pequeño , Ratas , Ratas Wistar , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
Anti-Thy1 nephritis is a well-established experimental mesangial proliferative nephritis model. Exploring the molecular mechanisms of pathophysiology in anti-Thy1 nephritis may elucidate the pathogeneses of mesangial proliferation. We examined the roles and acting mechanisms of differentially expressed proteins (DEPs) by bioinformatics analysis of glomeruli proteomic profiles during the course of anti-Thy1 nephritis. In total, 108 DEPs were found by two-dimensional fluorescence difference gel electrophoresis (2D-DIGE), and 40 DEPs were identified by matrix-assisted laser desorption ionization/time of flight and liquid chromatography-MS. DEPs were classified into five clusters (Clusters 1-5), according to their expression trends using Cluster 3.0 software, involved in regulating biological processes such as the stress response, cell proliferation, apoptosis, energy metabolism, transport, and the actin cytoskeleton. The expression patterns of ten DEPs, distributed across five clusters, including AKR1A1, AGAT, ATP6V1B2, HIBADH, MDH1, MPST, NIT2, PRDX6, PSMB7, and TPI1, were validated by Western blotting. Based on Western blotting and immunohistochemistry, we also found that the DEP FHL2, which was primarily expressed in the mesangial region, was down-regulated on days 3 and 5, and up-regulated on day 10. In vitro, we found that FHL2 overexpression induced mesangial cell proliferation by increasing the number of S-phase cells and decreasing G2/M-phase cells, whereas inhibiting FHL2 had the opposite effect. This study explored novel DEPs and their expression patterns during anti-Thy1 nephritis, and elucidated FHL2's effect on mesangial cell proliferation. These results will contribute to our understanding of the pathogenesis of mesangial proliferation.
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Proteínas con Homeodominio LIM/metabolismo , Células Mesangiales/citología , Proteínas Musculares/metabolismo , Nefritis/metabolismo , Factores de Transcripción/metabolismo , Animales , Proliferación Celular , Análisis por Conglomerados , Modelos Animales de Enfermedad , Isoanticuerpos , Proteínas con Homeodominio LIM/farmacología , Masculino , Células Mesangiales/efectos de los fármacos , Proteínas Musculares/farmacología , Nefritis/patología , Proteínas/metabolismo , Proteómica , Ratas , Ratas Wistar , Factores de Transcripción/farmacología , Electroforesis Bidimensional Diferencial en GelRESUMEN
BACKGROUND/AIMS: During the disease process of mesangial proliferative glomerulonephritis, the expression of various factors that influence mesangial proliferation is altered. MAX interactor 1 (Mxi1) antagonizes the transcription factor Myc and is believed to be a tumor suppressor. However, no studies have investigated its effect on mesangial cell proliferation. METHODS: To investigate the effect of Mxi1 on renal mesangial cell proliferation, we established a classic rat anti-Thy1 mesangial proliferative glomerulonephritis model. Mesangial proliferation was estimated by immunohistochemical analysis of Ki67. Mxi1 expression at each time point was assessed by real-time RT-PCR and Western blot analyses. Furthermore, we altered the expression level of Mxi1 by a plasmid and siRNA to detect its effect on rat mesangial cell proliferation in vitro. RESULTS: Mxi1 expression decreased significantly during the proliferative period of anti-Thy1 nephritis model and then gradually increased as proliferation declined, indicating that Mxi1 may be linked to mesangial cell proliferation. Upregulation of Mxi1 expression via plasmid transfection in vitro reduced the expression of the positive-acting cell cycle regulatory proteins cyclin B1, cyclin D1, cyclin E, CDC2 and CDK2; significantly reduced mesangial cell proliferation; reduced the percentage of S phase cells; and increased the percentage of G2/M phase cells. Inhibition of Mxi1 expression by siRNA in vitro produced the opposite effects: increased expression of cyclin B1, cyclin D1, cyclin E, CDC2 and CDK2; markedly increased cell proliferation; higher percentage of S phase cells; and dramatically lower percentage of G2/M phase cells. Transcription factor c-myc protein expression showed no obvious difference after Mxi1 plasmid and siRNA transfection. The expressions of cell cycle regulatory proteins mentioned above were negative correlated with Mxi1 expression in anti-Thy1 nephritis model. CONCLUSION: These results suggest that Mxi1 expression levels were inversely correlated with proliferation in anti-Thy1 nephritis rats and it may influence cell cycle progression and thus the rate of mesangial cell proliferation by regulating the expression of c-myc target cell cycle regulatory proteins.