Dataset Information

Intrinsic velocity differences between larynx raising and larynx lowering.

ABSTRACT: In this study, 23 subjects produced cyclic transitions between rounded vowels and unrounded vowels as in /o-i-o-i-o-…/ at two specific speaking rates. Rounded vowels are typically produced with a lower larynx position than unrounded vowels. This contrast in vertical larynx position was further amplified by producing the unrounded vowels with a higher pitch than the rounded vowels. The vertical larynx movements of each subject were measured by means of object tracking in laryngeal ultrasound videos. The results indicate that larynx lowering was on average 26% faster than larynx raising, and that this velocity difference was more pronounced in woman than in men. Possible reasons for this are discussed with a focus on specific biomechanical properties. The results can help to interpret vertical larynx movements with regard to underlying neural control and aerodynamic conditions, and to improve movement models for articulatory speech synthesis.

SUBMITTER: Kleiner C

PROVIDER: S-EPMC9934366 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Intrinsic velocity differences between larynx raising and larynx lowering.

Kleiner Christian C Häsner Patrick P Birkholz Peter P

PloS one 20230216 2

In this study, 23 subjects produced cyclic transitions between rounded vowels and unrounded vowels as in /o-i-o-i-o-…/ at two specific speaking rates. Rounded vowels are typically produced with a lower larynx position than unrounded vowels. This contrast in vertical larynx position was further amplified by producing the unrounded vowels with a higher pitch than the rounded vowels. The vertical larynx movements of each subject were measured by means of object tracking in laryngeal ultrasound vide ...[more]

PMID: 36795744

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Project description:BackgroundSAMHD1 mediates resistance to anti-cancer nucleoside analogues, including cytarabine, decitabine, and nelarabine that are commonly used for the treatment of leukaemia, through cleavage of their triphosphorylated forms. Hence, SAMHD1 inhibitors are promising candidates for the sensitisation of leukaemia cells to nucleoside analogue-based therapy. Here, we investigated the effects of the cytosine analogue CNDAC, which has been proposed to be a SAMHD1 inhibitor, in the context of SAMHD1.MethodsCNDAC was tested in 13 acute myeloid leukaemia (AML) cell lines, in 26 acute lymphoblastic leukaemia (ALL) cell lines, ten AML sublines adapted to various antileukaemic drugs, 24 single cell-derived clonal AML sublines, and primary leukaemic blasts from 24 AML patients. Moreover, 24 CNDAC-resistant sublines of the AML cell lines HL-60 and PL-21 were established. The SAMHD1 gene was disrupted using CRISPR/Cas9 and SAMHD1 depleted using RNAi, and the viral Vpx protein. Forced DCK expression was achieved by lentiviral transduction. SAMHD1 promoter methylation was determined by PCR after treatment of genomic DNA with the methylation-sensitive HpaII endonuclease. Nucleoside (analogue) triphosphate levels were determined by LC-MS/MS. CNDAC interaction with SAMHD1 was analysed by an enzymatic assay and by crystallisation.ResultsAlthough the cytosine analogue CNDAC was anticipated to inhibit SAMHD1, SAMHD1 mediated intrinsic CNDAC resistance in leukaemia cells. Accordingly, SAMHD1 depletion increased CNDAC triphosphate (CNDAC-TP) levels and CNDAC toxicity. Enzymatic assays and crystallisation studies confirmed CNDAC-TP to be a SAMHD1 substrate. In 24 CNDAC-adapted acute myeloid leukaemia (AML) sublines, resistance was driven by DCK (catalyses initial nucleoside phosphorylation) loss. CNDAC-adapted sublines displayed cross-resistance only to other DCK substrates (e.g. cytarabine, decitabine). Cell lines adapted to drugs not affected by DCK or SAMHD1 remained CNDAC sensitive. In cytarabine-adapted AML cells, increased SAMHD1 and reduced DCK levels contributed to cytarabine and CNDAC resistance.ConclusionIntrinsic and acquired resistance to CNDAC and related nucleoside analogues are driven by different mechanisms. The lack of cross-resistance between SAMHD1/ DCK substrates and non-substrates provides scope for next-line therapies after treatment failure.

Dataset Information

Intrinsic velocity differences between larynx raising and larynx lowering.

Publications

Intrinsic velocity differences between larynx raising and larynx lowering.

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