457 research outputs found

    Korean laryngeal contrast revisited:An electroglottographic study on denasalized and oral stops

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    In several Korean dialects, domain-initial nasal onsets undergo denasalization as a recent sound change. Nasal stops may be realized as prevoiced or even devoiced stops. This makes it necessary to examine the interplay of phonetic properties of the denasalized and the three oral stop series as a whole, in synchrony and diachrony. What are their concomitant and conflicting properties? Our study provides a bigger picture of the laryngeal contrast in Seoul and Gyeonggi Korean by examining the acoustic distributions related to the laryngeal properties of the four stop series, using acoustic and electroglottographic data. VOT and 'f'0 play important roles in the distinction of the four stop series, in line with previous studies. While the contribution of voice quality is relatively minor, we show that it plays an essential role of disambiguation when the VOT–'f'0 space gets crowded: When lenis stops can be confused with other stops, there is an enhancement of breathy voice. Finally, we discuss stop variation according to prosodic contexts. We highlight the basis of both syntagmatic variation and paradigmatic contrast in their phonetic implementations. They illustrate a constant reorganization to reconcile contrast maintenance with constraints from articulatory and perceptual systems, as well as language-specific structures

    VOT-F0 coarticulation in Japanese:Production-biased or misparsing?

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    International audienceIn production, word-initial voicing contrast of plosives in Tokyo Japanese is not robustly based on VOT, since young speakers tend to devoice previously voiced plosives. Meanwhile, speakers rely heavily on f0. The present study aims to examine the role of VOT and f0 cues in perception. We conducted an identification test using resynthesized stimuli along a VOT continuum (-60 to +40 ms) orthogonal to an f0 continuum. Results suggested a categorical perception of VOT, while f0 was especially useful when VOT was around 0 ms. Higher f0 contours affected the response rate more than lower f0 contours, suggesting that the perceptual role of f0 raising was more important than f0 lowering. Hence, plosive devoicing in production is not preceded by listeners' misparsing of low f0 and prevoicing. Their misattribution of high f0 to voicelessness may play a more important role in the shift of VOT-f0 cue weighting in perception and production

    Regulation of Adrenomedullin and its Family Peptide by RAMP System – Lessons from Genetically Engineered Mice

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    Adrenomedullin (ADM), originally identified as a vasodilating peptide, is now recognized to be a pleiotropic molecule involved in both the pathogenesis of cardiovascular diseases and circulatory homeostasis. Homozygotes of ADM knockout mice (ADM-/-) were lethal at mid-gestation with abnormalities of vascular development and this finding clarified the angiogenic potency of ADM. Calcitonin gene-related peptide (CGRP), which has a structure and function similar to that of ADM, has been identified as a family peptide of ADM. Unlike ADM-/-, CGRP-/- were apparently normal. Therefore, the study of knockout mice first clarified the distinctly different physiological roles between ADM and CGRP. In contrast, heterozygotes of ADM knockout mice (ADM+/-) were alive but showed blood pressure elevation, reduced neovascularization, and enhanced neointimal formation by arterial injury. Based on these observations, there was hope ADM would have a therapeutic use. However, ADM has a short half-life in the blood stream and its application in chronic disease has limitations. Therefore, we focused on the ADM receptor system. The calcitonin-receptor-like receptor (CLR), which is the ADM receptor, associates with one of the accessory proteins, called receptor activity-modifying proteins (RAMPs). By interacting with RAMP1, CLR exhibits a high affinity for CGRP, whereas by interacting with either RAMP2 or -3, CLR exhibits a high affinity for ADM. We generated RAMP knockout mice and found that vascular phenotypes similar to ADM-/- were reproduced only in RAMP2-/-. This shows that RAMP2 is the key determinant of the vascular functions of ADM. RAMP2 could be an attractive therapeutic target in cardiovascular diseases.ArticleCURRENT PROTEIN & PEPTIDE SCIENCE. 14(5):347-357 (2013)journal articl

    Significance of common variants on human chromosome 8q24 in relation to the risk of prostate cancer in native Japanese men

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    <p>Abstract</p> <p>Background</p> <p>Common variants on human chromosome 8q24, rs1447295 (C/A) and rs6983267 (T/G), have been recently linked to the prevalence of prostate cancer in European and American populations. Here, we evaluated whether the single-nucleotide polymorphisms rs1447295 and rs6983267 were associated with the risk of sporadic prostate cancer as well as latent prostate cancer in a native Japanese population.</p> <p>Results</p> <p>We analyzed genomic DNA samples from 391 sporadic prostate cancer patients, 323 controls who had died from causes unrelated to cancer and 112 Japanese men who were diagnosed as having latent prostate cancer based on autopsy results. The polymorphisms were determined by allelic discrimination using a fluorescent-based TaqMan assay. The A allele of rs1447295 was significantly associated with the risk of sporadic prostate cancer (<it>p </it>= 0.04; age-adjusted OR, 1.34), while the G allele of rs6983267 showed a trend towards being a high-risk allele (<it>p </it>= 0.06; age-adjusted OR, 1.27). No significant difference between these two polymorphisms and the risk of latent prostate cancer was observed in the present Japanese population.</p> <p>Conclusion</p> <p>Known variants on human chromosome 8q24 may be risk factors for sporadic prostate cancer in native Japanese men.</p

    Genetic analyses of novel compound heterozygous hypodysfibrinogenemia, Tsukuba I: FGG c.1129+62_65 del AATA and FGG c.1299+4 del A

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    Epub 2016 Nov 5Introduction: Wefound a novel hypodysfibrinogenemia designated Tsukuba I caused by compound heterozygous nucleotide deletionswith FGG c. 1129+ 62_ 65 del AATA and FGG c. 1299+ 4 del A on different alleles. The former was deep in intron 8 of FGG (IVS-8 deletion) and the latter in exon 9 of FGG (Ex-9 deletion), which is translated for the gamma'-chain, but not the.A-chain. AWestern blot analysis of plasma fibrinogen from our patient revealed an aberrant gamma-chain that migrated slightly faster than the normal B beta-chain. Materials andmethods: To clarify the complex genetic mechanismunderlying Tsukuba I's hypodysfibrinogenemia induced by nucleotide deletions in two regions, we generated two minigenes incorporating each deletion region, transfected them into Chinese Hamster Ovary (CHO) cells, and analyzed RT-PCR products. We also established CHO cells producing the recombinant variant fibrinogen,gamma' 409.A (Ex-9 deletion). Results and conclusions: Minigene I incorporating the IVS-8 deletion showed two products: a normal splicing product and the unspliced product. Minigene II incorporating the Ex-9 deletion only produced the unspliced product. The established gamma' 409.A-CHOcells secreted variant fibrinogenmore effectively than normal fibrinogen. Therefore, the aberrant splicing products derived from the IVS-8 deletion cause hypofibrinogenemia most likely due to nonsense-mediated mRNA decay and the partial production of normal.A-and gamma'-chains; moreover, the Ex-9 deletion causes hypodysfibrinogenemia due to the absence of normal.A-and gamma'-chain production (hypofibrinogenemia) and augmented aberrant.'-chain production (dysfibrinogenemia). (C) 2016 Elsevier Ltd. All rights reserved.ArticleTHROMBOSIS RESEARCH. 148:111-117 (2016)journal articl

    The fibrous form of intracellular inclusion bodies in recombinant variant fibrinogen-producing cells is specific to the hepatic fibrinogen storage disease-inducible variant fibrinogen

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    Fibrinogen storage disease (FSD) is a rare disorder that is characterized by the accumulation of fibrinogen in hepatocytes and induces liver injury. Six mutations in the γC domain (γG284R, γT314P, γD316N, the deletion of γG346-Q350, γG366S, and γR375W) have been identified for FSD. Our group previously established γ375W fibrinogen-producing Chinese hamster ovary (CHO) cells and observed aberrant large granular and fibrous forms of intracellular inclusion bodies. The aim of this study was to investigate whether fibrous intracellular inclusion bodies are specific to FSD-inducible variant fibrinogen. Thirteen expression vectors encoding the variant γ-chain were stably or transiently transfected into CHO cells expressing normal fibrinogen Aα- and Bβ-chains or HuH-7 cells, which were then immunofluorescently stained. Six CHO and HuH-7 cell lines that transiently produced FSD-inducible variant fibrinogen presented the fibrous (3.2?22.7 and 2.1?24.5%, respectively) and large granular (5.4?25.5 and 7.7?23.9%) forms of intracellular inclusion bodies. Seven CHO and HuH-7 cell lines that transiently produced FSD-non-inducible variant fibrinogen only exhibit the large granular form. These results demonstrate that transiently transfected variant fibrinogen-producing CHO cells and inclusion bodies of the fibrous form may be useful in non-invasive screening for FSD risk factors for FSD before its onset.ArticleINTERNATIONAL JOURNAL OF HEMATOLOGY.105:758-768(2017)journal articl
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