Search

Purpose: The aim of this study was to assess the frequency and types of compensatory articulations (CAs) in nonsyndromic patients with velopharyngeal dysfunction (VPD) and various palatal anomalies and to determine the relationship between the frequency of CAs, type of palatal anomaly, and phonological errors. Method: A total of 783 nonsyndromic, Hebrew-speaking patients with VPD and various palatal anomalies (cleft lip and palate [CLP], cleft palate [CP], submucous CP [SMCP], occult submucous Cp [OSMCP], or non-CP) were studied retrospectively. Perceptual VPD tests, including articulation and phonological assessment, were conducted. CAs were described as below the level of the defect in the vocal tract (abnormal backing of oral targets to post-uvular place) or in front of it within the oral cavity (palatalization) and at the velopharyngeal port. Results: Among 783 patients, 213 (27.2%) had CAs. Most CAs (18.4%) occurred below the level of the defect, followed by CAs at the velopharyngeal port (12.0%) or in front of it (4.9%). No differences were found in the frequency of CAs between patients with CP (47.8%) or CLP (52.6%) and between those with non-CP (13.6%) or OSMCP (14.7%). SMCP patients had lower frequency of CAs (29.8%) than CP (p = .003) and CLP (p = .002) patients but higher frequency than OSMCP (p = .002) and non-CP (p = .002) patients did. Among the 783 patients, 247 (31.5%) had phonological errors. A higher frequency of phonological errors was found in patients with CAs (55.4%) compared to those without (22.6%) and in all palatal anomaly groups except CLP (31.4% vs. 23.9%). Conclusions: CAs in nonsyndromic patients with VPD remained relatively high in all age groups, up to adulthood. CAs are influenced by inadequate velar length following palatal repair, as well as by oral structural abnormalities, whereas poor muscle function due to OSMCP and/or abnormal size and/or shape of nasopharynx has less influence. Errors produced in front of the velopharyngeal port are influenced by the structural anomaly of CLP. This information may contribute to general phonetic and phonological theories and genetic investigations about CP anomalies., Palatal anomalies comprise a group of structural disorders that can affect speech intelligibility and communicative functions. Acceptably intelligible speech contributes to patients' functioning in society, and it is often evaluated [...]

Purpose: We examined the effect of bite block insertion (BBI) on lingual movements and formant frequencies in corner vowel and diphthong production in a sentence context. Method: Twenty young adults produced the corner vowels (/u/, /a/, /ae/, /i/) and the diphthong /ai/ in sentence contexts before and after BBI. An electromagnetic articulograph measured the movements of the tongue back, middle, and front. Results: There were significant decreases in the acoustic vowel articulation index and vowel space area following BBI. The kinematic vowel articulation index decreased significantly for the back and middle of the tongue but not for the front. There were no significant acoustic changes post-BBI for the diphthong, other than a longer transition duration. Diphthong kinematic changes after BBI included smaller movements for the back and middle of the tongue, but not the front. Conclusions: BBI led to a smaller acoustic working space for the corner vowels. The adjustments made by the front of the tongue were sufficient to compensate for the BBI perturbation in the diphthong, resulting in unchanged formant trajectories. The back and middle of the tongue were likely biomechanically restricted in their displacement by the fixation of the jaw, whereas the tongue front showed greater movement flexibility., The accurate production of speech sounds requires that speakers regulate the speed, force, and timing of articulatory movements. Because of the complexity involved, even seemingly small disturbances to the system [...]

Purpose: This study compared attention control and flexibility in school-age children who stutter (CWS) and children who do not stutter (CWNS) based on their performance on a behavioral task and parent report. We used a classic attention-shifting paradigm that included manipulations of task goals and timing to test effects of varying demands for flexibility on switching accuracy and speed. We also examined associations between task performance, group, and relevant aspects of temperament. Method: Participants included 33 children (15 CWS, 18 CWNS) between 8 and 11 years of age. Children sorted stimuli that differed on two dimensions (color and shape) based on sorting rules that varied from block to block or trial to trial. Timing manipulations included intervals of 200-, 600-, or 1,200-ms durations for critical trial components. Temperament data were obtained via the Children's Behavior Questionnaire. Results: All children showed expected performance costs in response to block and trial manipulations; however, CWS were more affected by task conditions that increased demands for cognitive flexibility. Effects of interval durations also differed by group. Factor scores on the Children's Behavior Questionnaire indicated differences in effortful control between groups; however, this aspect of temperament did not mediate between-groups differences in switching performance. Conclusions: Findings suggest that stuttering continues to be associated with differences in attention control and flexibility beyond the preschool years. Further research is needed to clarify how these cognitive processes shape the development of stuttering throughout childhood., Attention is a basic building block for emerging executive functions (EFs; Blair & Ursache, 2011). The ability to focus attention on task-relevant stimuli or goals and switch attention flexibly from [...]

Protein structure prediction can be used to determine the three-dimensional shape of a protein from its amino acid sequence.sup.1. This problem is of fundamental importance as the structure of a protein largely determines its function.sup.2; however, protein structures can be difficult to determine experimentally. Considerable progress has recently been made by leveraging genetic information. It is possible to infer which amino acid residues are in contact by analysing covariation in homologous sequences, which aids in the prediction of protein structures.sup.3. Here we show that we can train a neural network to make accurate predictions of the distances between pairs of residues, which convey more information about the structure than contact predictions. Using this information, we construct a potential of mean force.sup.4 that can accurately describe the shape of a protein. We find that the resulting potential can be optimized by a simple gradient descent algorithm to generate structures without complex sampling procedures. The resulting system, named AlphaFold, achieves high accuracy, even for sequences with fewer homologous sequences. In the recent Critical Assessment of Protein Structure Prediction.sup.5 (CASP13)--a blind assessment of the state of the field--AlphaFold created high-accuracy structures (with template modelling (TM) scores.sup.6 of 0.7 or higher) for 24 out of 43 free modelling domains, whereas the next best method, which used sampling and contact information, achieved such accuracy for only 14 out of 43 domains. AlphaFold represents a considerable advance in protein-structure prediction. We expect this increased accuracy to enable insights into the function and malfunction of proteins, especially in cases for which no structures for homologous proteins have been experimentally determined.sup.7. AlphaFold predicts the distances between pairs of residues, is used to construct potentials of mean force that accurately describe the shape of a protein and can be optimized with gradient descent to predict protein structures., Author(s): Andrew W. Senior [sup.1] , Richard Evans [sup.1] , John Jumper [sup.1] , James Kirkpatrick [sup.1] , Laurent Sifre [sup.1] , Tim Green [sup.1] , Chongli Qin [sup.1] , [...]

Purpose: Our knowledge of speech rate development remains inadequate because of limited longitudinal data and lack of data from children under age 3;0 (years; months). The purpose of this longitudinal study was to test the pattern of speech rate development between ages 2;0 and 3;0. Method: Speech rate was assessed at 4 time points between ages 2;0 and 3;0. The analysis employed multilevel models to characterize the development of speech rate (syllables per second), phonemes per second (PPS), length of active declarative sentences, and mean length of utterance. Results: The results indicate a significant linear increase in speech rate, PPS, length of active declarative sentences, and mean length of utterance occurring over the 1-year period. Male and female children differed in speech rate, PPS, and utterance length, suggesting sex is a potential factor in early speech rate development. Conclusions: Our findings indicate that the speech motor system develops rapidly during the period when grammar emerges. Speech rate has the potential to be an important metric for understanding typical speech development and speech disorders., The rate of speech is a product of several factors including sensorimotor and language processes (e.g., Allen, 1973; Kent, 1976, 2004; Nip & Green, 2013; Redford, 2015). As these factors [...]

Purpose: The purpose of this study was to assess changes in autonomic, behavioral, and acoustic measures in response to social stress in adults who stutter (AWS) compared to adults who do not stutter (ANS). Method: Participants completed the State-Trait Anxiety Inventory (Speilberger, Gorsuch, Luschene, Vagg, & Jacobs, 1983). In order to provoke social stress, participants were required to complete a modified version of the Trier Social Stress Test (TSST-M, Kirschbaum, Pirke, & Hellhammer, 1993), which included completing a nonword reading task and then preparing and delivering a speech to what was perceived as a group of professionals trained in public speaking. Autonomic nervous system changes were assessed by measuring skin conductance levels, heart rate, and respiratory sinus arrhythmia (RSA). Behavioral changes during speech production were measured in errors, percentage of syllable stuttered, percentage of other disfluencies, and speaking rate. Acoustic changes were measured using 2nd formant frequency fluctuations. In order to make comparisons of speech with and without social-cognitive stress, measurements were collected while participants completed a speaking task before and during TSST-M conditions. Results: AWS showed significantly higher levels of self-reported state and trait anxiety compared to ANS. Autonomic nervous system changes revealed similar skin conductance level and heart rate across pre-TSST-M and TSST-M conditions; however, RSA levels were significantly higher in AWS compared to ANS across conditions. There were no differences found between groups for speaking rate, fundamental frequency, and percentage of other disfluencies when speaking with or without social stress. However, acoustic analysis revealed higher levels of 2nd formant frequency fluctuations in the AWS compared to the controls under pre-TSST-M conditions, followed by a decline to a level that resembled controls when speaking under the TSST-M condition. Discussion: Results suggest that AWS, compared to ANS, engage higher levels of parasympathetic control (i.e., RSA) during speaking, regardless of stress level. Higher levels of self-reported state and trait anxiety support this view point and suggest that anxiety may have an indirect role on articulatory variability in AWS., The neurophysiological underpinnings to developmental stuttering have been largely studied with focuses in emotion (e.g., Bowers, Saltuklaroglu, & Kalinwoski, 2012; Choi, Conture, Walden, Jones, & Kim, 2016; Jones et al., [...]

An important component of cellular biochemistry is the concentration of proteins and nucleic acids in non-membranous compartments.sup.1,2. These biomolecular condensates are formed from processes that include liquid-liquid phase separation. The multivalent interactions necessary for liquid-liquid phase separation have been extensively studied in vitro.sup.1,3. However, the regulation of this process in vivo is poorly understood. Here we identify an in vivo regulator of liquid-liquid phase separation through a genetic screen targeting factors required for Arabidopsis RNA-binding protein FCA function. FCA contains prion-like domains that phase-separate in vitro, and exhibits behaviour in vivo that is consistent with phase separation. The mutant screen identified a functional requirement for FLL2, a coiled-coil protein, in the formation of FCA nuclear bodies. FCA reduces transcriptional read-through by promoting proximal polyadenylation at many sites in the Arabidopsis genome.sup.3,4. FLL2 was required to promote this proximal polyadenylation, but not the binding of FCA to target RNA. Ectopic expression of FLL2 increased the size and number of FCA nuclear bodies. Crosslinking with formaldehyde captured in vivo interactions between FLL2, FCA and the polymerase and nuclease modules of the RNA 3'-end processing machinery. These 3' RNA-processing components colocalized with FCA in the nuclear bodies in vivo, which indicates that FCA nuclear bodies compartmentalize 3'-end processing factors to enhance polyadenylation at specific sites. Our findings show that coiled-coil proteins can promote liquid-liquid phase separation, which expands our understanding of the principles that govern the in vivo dynamics of liquid-like bodies. A genetic screen for factors required by the Arabidopsis RNA-binding protein FCA identifies FLL2 as necessary in the formation of FCA nuclear bodies, and thus a role for FLL2 in liquid-liquid phase separation., Author(s): Xiaofeng Fang [sup.1] , Liang Wang [sup.2] , Ryo Ishikawa [sup.1] [sup.5] , Yaoxi Li [sup.1] , Marc Fiedler [sup.3] , Fuquan Liu [sup.1] [sup.6] , Grant Calder [sup.1] [...]

Normal hematopoiesis is sustained through a carefully orchestrated balance between hematopoietic stem cell (HSC) self-renewal and differentiation. The functional importance of this axis is underscored by the severity of disease phenotypes initiated by abnormal HSC function, including myelodysplastic syndromes and hematopoietic malignancies. Major advances in the understanding of transcriptional regulation of primitive hematopoietic cells have been achieved; however, the post-transcriptional regulatory layer that may impinge on their behavior remains underexplored by comparison. Key players at this level include RNA-binding proteins (RBPs), which execute precise and highly coordinated control of gene expression through modulation of RNA properties that include its splicing, polyadenylation, localization, degradation, or translation. With the recent identification of RBPs having essential roles in regulating proliferation and cell fate decisions in other systems, there has been an increasing appreciation of the importance of post-transcriptional control at the stem cell level. Here we discuss our current understanding of RBP-driven post-transcriptional regulation in HSCs, its implications for normal, perturbed, and malignant hematopoiesis, and the most recent technological innovations aimed at RBP-RNA network characterization at the systems level. Emerging evidence highlights RBP-driven control as an underappreciated feature of primitive hematopoiesis, the greater understanding of which has important clinical implications.Key words: hematopoietic stem cells, leukemia stem cells, post-transcriptional regulation, RNA-binding proteins, RNA regulons.L'hematopoiese normale est soutenue par un equilibre soigneusement orchestre entre l'autorenouvelement des cellules souches hematopoietiques (CSH) et leur differenciation. L'importance fonctionnelle de cet axe est mise en evidence par la severite des phenotypes des maladies initiees par une fonction anormale des CSH, dont les syndromes myelodysplasiques et les cancers hematopoietiques. Des percees importantes dans la comprehension de la regulation transcriptionnelle des cellules hematopoietiques primitives ont ete realisees; toutefois, en comparaison, les composantes de la regulation post-transcriptionnelle qui pourraient affecter leur comportement demeurent peu explorees. Les joueurs cles de ce niveau de regulation comprennent les proteines de liaison de l'ARN qui executent un controle hautement coordonne de l'expression genique par la modulation des proprietes de l'ARN dont l'epissage, la polyadenylation, la localisation, la degradation ou la traduction. Avec l'identification recente de proteines de liaison de l'ARN qui jouent un role essentiel dans la regulation de la proliferation et des decisions cellulaires dans d'autres systemes, l'importance du controle post-transcriptionnel a l'echelle des cellules souches est de plus en plus reconnue. Les auteurs discutent ici de la comprehension actuelle de la regulation post-transcriptionnelle assuree par les proteines de liaison de l'ARN dans les CSH, de son implication dans l'hematopoiese normale, perturbee et maligne, de meme que des innovations technologiques les plus recentes visant a caracteriser le reseau ARN-proteines de liaison de l'ARN a l'echelle des systemes. De nouvelles donnees soulignent que le controle exerce par les proteines de liaison de l'ARN constitue une caracteristique negligee de l'hematopoiese primitive, dont une meilleure connaisance aurait d'importantes retombees cliniques. [Traduit par la Redaction]Mots-cles : cellules souches hematopoietiques, cellules souches leucemiques, regulation post-transcriptionnelle, proteines de liaison de l'ARN, regulons d'ARN., IntroductionThe machinery underlying stem cells' capacity to orchestrate their self-maintenance and differentiation can be represented as integrated circuits that are genetically programmed. As demonstrated by the capacity to reprogram somatic [...]

Purpose: This study investigated the effects of an intervention to reduce caregivers' articulation rates with children who stutter on (a) disfluency, (b) caregiver and child's articulation rates, and (c) caregiver and child's response time latency (RTL). Method: Seventeen caregivers and their preschool children who stuttered participated in a group study of treatment outcomes. One speech sample was collected as a baseline, and 2 samples were collected after treatment. Post-treatment samples were of caregivers speaking as they typically would and using reduced articulation rates. Results: Caregivers reduced articulation rates significantly in the 2 posttreatment samples, and a significant decrease of stuttering-like disfluencies (SLD) was found in the children in those 2 samples. No direct relationship was found between the caregiver's articulation rate and RTL, and there was a small correlation of RTL with the lower levels of SLD found postintervention. No significant relationships were found between the reduced levels of SLD and articulation rates for either caregivers or children. Conclusions: Results suggest caregivers can be trained to slow their speech, and children increased their fluency at the end of a program designed to slow caregiver articulation. The intentionally slower rate of the caregivers, however, was not significantly related to fluency., It has become standard practice among speech-language pathologists to provide some level of parent counseling for the treatment of stuttering in preschool children. Intervention strategies aimed at parents may range [...]

Purpose: The purpose of this study was to ascertain if there is an association between stuttering severity and behaviors and the expression of temperament characteristics, including precursors of anxiety. Method: We studied temperament characteristics of a prospectively recruited community cohort of children who stutter (N = 173) at ages 3, 4, and 6 years using the Short Temperament Scale STS (Prior, Sanson, Smart & Oberklaid, 2000). Results: Six of 131 statistical tests of association between stuttering severity and behaviors and temperament traits were statistically significant at the 5% level, which was no more than expected by chance alone. Conclusions: On the basis of parent responses to the STS, preschoolers who exhibited different levels of stuttering severity and behaviors did not generally express temperament traits differently from one another. Stuttering severity and stuttering behaviors were not associated with the precursors of anxiety. Overall, taking multiple tests into consideration, results show little evidence of association between stuttering severity and temperament up to 4 years of age or between stuttering behaviors and temperament up to 6 years of age., Temperament refers to the way a person responds to and interacts with the environment. Temperament is stable and genetically determined (Buss & Plomin, 1984; Costa & McCrae, 2001; Goldsmith, 1996; [...]

Abstract: With the functional importance of alternative splicing being validated in nearly every mammalian biological system and implicated in many human diseases, it is now crucial to identify the molecular [...]

MicroRNAs (miRNAs) are short, non-coding RNAs that employ classic Watson-Crick base-pairing to identify their target genes, ultimately resulting in destabilization of their target mRNAs and/or inhibition of their translation. The role of miRNAs in a wide range of human diseases, including those afflicting the kidney, has been intensely investigated. However, there is still a vast dearth of knowledge regarding their specific mode of action and therapeutic effects in various kidney diseases. This review discusses the latest efforts to further our understanding of the basic biology of miRNAs, their impact on various kidney diseases and their potential as novel biomarkers and therapeutic agents. We initially provide an overview of miRNA biology and the canonical pathway implicated in their biogenesis. We then discuss commonly employed experimental strategies for miRNA research and highlight some of the newly described state-of-the-art technologies to identify miRNAs and their target genes. Finally, we carefully examine the emerging role of miRNAs in the pathogenesis of various kidney diseases., Author(s): Shawn S. Badal[sup.1] [sup.2] , Farhad R. Danesh[sup.1] [sup.2] [sup.3] Author Affiliations: (1) Section of Nephrology, The University of Texas at MD Anderson Cancer Center, 1400 Pressler Street, Unit [...]

This study presents the results of an empirical investigation of attitudes toward bribe taking in Egypt. The authors use the Human Beliefs and Values Survey data to examine several demographic variables to determine whether demographics make a difference. The total sample size was over 3000. The study found that some demographic variables do make a difference. Keywords: Bribe, Egypt, demographic variables, gender, age, religion, employment status, marital status, education level, social class, happiness, health, political spectrum, INTRODUCTION Bribery has been around for thousands of years. In some societies it is an accepted way of doing business, and is viewed either as a means of greasing the [...]

Purpose: Early childhood stuttering is associated with atypical speech motor development. Compared with children who do not stutter (CWNS), the speech motor systems of school-age children who stutter (CWS) may also be particularly susceptible to breakdown under increased processing demands. The effects of increased syntactic complexity and sentence length on articulatory coordination were investigated. Method: Kinematic, temporal, and behavioral indices of articulatory coordination were quantified for school-age CWS (n = 19) and CWNS (n = 18). Participants produced 4 sentences varying in syntactic complexity (simple declarative/complex declarative with a relative clause) and sentence length (short/long). Lip aperture variability (LAVar) served as a kinematic measure of interarticulatory consistency over repeated productions. Articulation rate (syllables per second) was also calculated as a related temporal measure. Finally, we computed accuracy and stuttering frequency percentages for each sentence to assess task performance. Results: Increased sentence length, but not syntactic complexity, increased LAVar in both groups. This effect was disproportionately greater for CWS compared with CWNS. No group differences were observed for articulation rate. CWS were also less accurate in their sentence productions than fluent peers and exhibited more instances of stuttering when processing demands associated with length and syntactic complexity increases. Conclusions: The speech motor systems of school-age CWS appear to be particularly vulnerable to processing demands associated with increased sentence length, as evidenced by increased LAVar. Increasing the length and complexity of the sentence stimuli also resulted in reduced production accuracy and increased stuttering frequency. We discuss these findings within a motor control framework of speech production., Childhood stuttering, also known as childhood-onset fluency disorder (American Psychiatric Association, 2013), is characterized by the presence of involuntary stuttering-like disfluencies (SLDs) that likely arise because of disruptions in the [...]