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PubMed2006

Dynamic expression of retinoic acid-synthesizing and -metabolizing enzymes in the developing mouse inner ear.

Retinoic acid signaling plays essential roles in morphogenesis and neural development through transcriptional regulation of downstream target genes. It is believed that the balance between the activities of synthesizing and metabolizing enzymes determines the amount of active retinoic acid to which a developing tissue is exposed. In this study, we investigated spatiotemporal expression patterns of four synthesizing enzymes, the retinaldehyde dehydrogenases 1, 2, 3, and 4 (Raldh1, Raldh2, Raldh3, and Raldh4) and two metabolizing enzymes (Cyp26A1 and Cyp26B1) in the embryonic and postnatal mouse inner ear by using quantitative reverse transcriptase polymerase chain reaction (RT-PCR), in situ hybridization, and Western blot analysis. Quantitative RT-PCR analysis and Western blot data revealed that the expression of CYP26s was much higher than that of Raldhs at early embryonic ages but that Cyp26 expression was downregulated during embryonic development. Conversely, the expression levels of Raldh2 and -3 increased during development and were significantly higher than the Cyp26 levels at postnatal day 20. At this age, Raldh3 was expressed predominantly in the cochlea, whereas Raldh2 was present in the vestibular end organ. At early embryonic stages, as observed by in situ hybridization, the synthesizing enzymes were expressed only in the dorsoventral epithelium of the otocyst, whereas the metabolizing enzymes were present mainly in mesenchymal cells surrounding the otic epithelium. At later stages, Raldh2, Raldh3, and Cyp26B1 were confined to the stria vascularis, spiral ganglion, and supporting cells in the cochlear and vestibular epithelia, respectively. The downregulation of Cyp26s and the upregulation of Raldhs after birth during inner ear maturation suggest tissue changes in the sensitivity to retinoic acid concentrations.

Aldehyde Oxidoreductases↗
PubMed2026

Toward real-time quantification of driving risks: a systematic review and research agenda of risk field theory.

In complex traffic systems, driving risk often evolves in a continuous and progressive manner prior to crash occurrence. How to effectively represent and analyze such latent risk states remains a central challenge in traffic safety research. In recent years, risk field-based approaches have introduced spatial and spatiotemporal continuous modeling paradigms, providing new perspectives for characterizing the distribution of traffic risk and its dynamic evolution. Motivated by the rapid growth of this research area and the lack of a systematic synthesis, this paper presents a comprehensive review of studies applying risk field theory to driving safety and traffic risk analysis. Following the PRISMA guidelines, relevant literature was collected through multi-database searches and analyzed using a combination of bibliometric analysis and qualitative review. The review systematically summarizes the theoretical foundations, modeling elements, data sources, analytical methods, and application domains of risk field-related research. Particular attention is given to studies that conceptualize traffic risk as a continuous field, complemented by a broader review of traffic risk factor literature to identify key elements and analytical dimensions involved in risk field modeling. On this basis, the paper synthesizes research progress in major application areas, including traffic safety state representation, driving behavior analysis, traffic conflict assessment, and autonomous driving and human-machine cooperative systems. Differences and commonalities among existing studies are compared in terms of modeling strategies, data support, and application scenarios. Through this systematic review, the paper clarifies the main research themes and methodological trends of risk field-based studies, providing a structured framework for understanding the evolution and application of this approach and offering methodological insights for risk perception modeling and safety-oriented decision support in intelligent transportation systems (ITS).

Humans↗
PubMed2002

Human chromosome 21 gene expression atlas in the mouse.

Genome-wide expression analyses have a crucial role in functional genomics. High resolution methods, such as RNA in situ hybridization provide an accurate description of the spatiotemporal distribution of transcripts as well as a three-dimensional 'in vivo' gene expression overview. We set out to analyse systematically the expression patterns of genes from an entire chromosome. We chose human chromosome 21 because of the medical relevance of trisomy 21 (Down's syndrome). Here we show the expression analysis of all identifiable murine orthologues of human chromosome 21 genes (161 out of 178 confirmed human genes) by RNA in situ hybridization on whole mounts and tissue sections, and by polymerase chain reaction with reverse transcription on adult tissues. We observed patterned expression in several tissues including those affected in trisomy 21 phenotypes (that is, central nervous system, heart, gastrointestinal tract, and limbs). Furthermore, statistical analysis suggests the presence of some regions of the chromosome with genes showing either lack of expression or, to a lesser extent, co-expression in specific tissues. This high resolution expression 'atlas' of an entire human chromosome is an important step towards the understanding of gene function and of the pathogenetic mechanisms in Down's syndrome.

Animals↗
PubMed2000

Fas ligand expression coincides with alveolar cell apoptosis in late-gestation fetal lung development.

Apoptosis plays a central role in the cellular remodeling of the developing lung. We determined the spatiotemporal patterns of the cell death regulators Fas and Fas ligand (FasL) during rabbit lung development and correlated their expression with pulmonary and type II cell apoptosis. Fetal rabbit lungs (25-31 days gestation) were assayed for apoptotic activity by terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) and DNA size analysis. Fas and FasL expression were analyzed by RT-PCR, immunoblot, and immunohistochemistry. Type II cell apoptosis increased significantly on gestational day 28; the type II cell apoptotic index increased from 0.54 +/- 0.34% on gestational day 27 to 3.34 +/- 1.24% on day 28, P < 0.01 (ANOVA). This corresponded with the transition from the canalicular to the terminal sac stage of development. The day 28 rise in epithelial apoptosis was synchronous with a robust if transient 20-fold increase in FasL mRNA and a threefold increase in FasL protein levels. In contrast, Fas mRNA levels remained constant, suggestive of constitutive expression. Fas and FasL proteins were immunolocalized to alveolar type II cells and bronchiolar Clara cells. The correlation of this highly specific pattern of FasL expression with alveolar epithelial apoptosis and remodeling implicates the Fas/FasL system as a potentially important regulatory pathway in the control of postcanalicular alveolar cytodifferentiation.

Animals↗
PubMed2004

The derivation of direction selectivity in the striate cortex.

In the central visual pathway of binocular animals, the property of directional selectivity (DS) is first exhibited in striate cortex. In this study, we sought to determine the neural circuitry underlying the transformation from non-DS neurons to DS cortical cells. In a well established model, DS receptive fields (RFs) are derived from the sum of two non-DS inputs with 90 degrees (quadrature) spatiotemporal phase differences. We explored possible input sources for this model, which include non-DS simple cells and lateral geniculate nucleus (LGN) neurons, by examination of spatiotemporal RFs of single cells and of pairs of cells. We find that distributions of non-DS simple RFs do not match the temporal predictions of the quadrature model because of a lack of long-latency responses. The long-latency inputs could potentially arise from lagged LGN afferents. However, analysis of cell pairs indicates that DS cells receive cortical input from non-DS simple cells for both short- and long-latency components, with temporal phase differences typically <90 degrees. Furthermore, the distribution of minimum phase differences needed to generate DS cells overlaps that exhibited by non-DS simple cells. Considered together, these results are consistent with a linear model whereby DS simple cells are formed from simple-cell inputs, with temporal phase differences often less than quadrature.

Animals↗
PubMed2006

The influence of hitchhiking and deleterious mutation upon asexual mutation rates.

The question of how natural selection affects asexual mutation rates has been considered since the 1930s, yet our understanding continues to deepen. The distribution of mutation rates observed in natural bacteria remains unexplained. It is well known that environmental constancy can favor minimal mutation rates. In contrast, environmental fluctuation (e.g., at period T) can create indirect selective pressure for stronger mutators: genes modifying mutation rate may "hitchhike" to greater frequency along with environmentally favored mutations they produce. This article extends a well-known model of Leigh to consider fitness genes with multiple mutable sites (call the number of such sites alpha). The phenotypic effect of such a gene is enabled if all sites are in a certain state and disabled otherwise. The effects of multiple deleterious loci are also included (call the number of such loci gamma). The analysis calculates the indirect selective effects experienced by a gene inducing various mutation rates for given values of alpha, gamma, and T. Finite-population simulations validate these results and let us examine the interaction of drift with hitchhiking selection. We close by commenting on the importance of other factors, such as spatiotemporal variation, and on the origin of variation in mutation rates.

Models, Genetic↗
PubMed2003

Expression of complement 3 and complement 5 in newt limb and lens regeneration.

Some urodele amphibians possess the capacity to regenerate their body parts, including the limbs and the lens of the eye. The molecular pathway(s) involved in urodele regeneration are largely unknown. We have previously suggested that complement may participate in limb regeneration in axolotls. To further define its role in the regenerative process, we have examined the pattern of distribution and spatiotemporal expression of two key components, C3 and C5, during limb and lens regeneration in the newt Notophthalmus viridescens. First, we have cloned newt cDNAs encoding C3 and C5 and have generated Abs specifically recognizing these molecules. Using these newt-specific probes, we have found by in situ hybridization and immunohistochemical analysis that these molecules are expressed during both limb and lens regeneration, but not in the normal limb and lens. The C3 and C5 proteins were expressed in a complementary fashion during limb regeneration, with C3 being expressed mainly in the blastema and C5 exclusively in the wound epithelium. Similarly, during the process of lens regeneration, C3 was detected in the iris and cornea, while C5 was present in the regenerating lens vesicle as well as the cornea. The distinct expression profile of complement proteins in regenerative tissues of the urodele lens and limb supports a nonimmunologic function of complement in tissue regeneration and constitutes the first systematic effort to dissect its involvement in regenerative processes of lower vertebrate species.

Amino Acid Sequence↗
PubMed2002

Spatiotemporal expression patterns of N-syndecan, a transmembrane heparan sulfate proteoglycan, in developing retina.

PURPOSE: N-syndecan is a transmembrane heparan sulfate proteoglycan, that is highly expressed in neural tissues. In the current study, changes in N-syndecan expression during retinal development were examined. METHODS: Localization of N-syndecan in developing rat retina was examined by immunohistochemistry and in situ hybridization. The amount of the core protein was evaluated by immunoblot analysis, using retinal homogenates at various developmental stages. In addition, mRNA expression was semiquantified by reverse transcription-polymerase chain reaction (RT-PCR). To understand better the localization of N-syndecan in retinal neuronal cells, we performed immunocytochemistry using retinal ganglion cells in culture. RESULTS: N-syndecan is highly expressed in nerve fiber-rich layers of the retina at early postnatal stages (between postnatal day [P]0 and P14). In contrast, immunoreactivity was faint during embryonic stages and late postnatal stages. In addition, in retinal flatmounted sections, N-syndecan immunoreactivity was observed on the axons of retinal ganglion cells. Intense signals were observed in the ganglion cell layer during in situ hybridization. Immunoblot analyses demonstrated that the amount of N-syndecan core protein reached a peak at approximately P14. The RT-PCR analyses using N-syndecan primers showed that an intense amplified band was observed in the cDNA derived from P14 retinas, whereas only faint bands were detected in the embryonic day (E)16 and P42 retinas. In retinal ganglion cells in culture, N-syndecan was located on the long, extended neurites. CONCLUSIONS: The data show that N-syndecan is transiently expressed, primarily in retinal neural fibers, during retinal development, indicating that it may be involved in formation of the retinal neural network.

Animals↗
PubMed1993

The RF-cinematogram. A cross-correlation technique for mapping several visual receptive fields at once.

We present a spike-triggered averaging method capable of mapping the visual receptive fields of several neurons simultaneously. The stimulation is general and the mapping proceeds automatically without the need to match the stimulation to the cells' preference for position, orientation, direction, etc. The maps are spatiotemporal; receptive field (RF) structures are quantitatively determined in three dimensions: the two dimensions of visuotopic space, and time. The method presented is one of a family of "reverse correlation" or "spike-triggered averaging" techniques (DeBoer and Kuyper 1968) capable of revealing linear aspects of stimulus-response coupling. The formal relationship of these methods to stimulus-response cross-correlation is shown. The analysis is extended to provide some second-order axis-of-motion information ("direction marks"). The stimulus is a constantly illuminated, randomly jumping bright or dark spot, not an elongated bar. Spot diameters between one-third to 1 x RF width are effective. The method ascertains for each recorded action potential or "spike" the prior visual field position of the spot. The average or most probable spot positions define the receptive field spatially. Repeating the process for a succession of times prior to observed spikes defines the field temporally, presented here as a succession of spatial maps. We term this portrayal a receptive field cinematogram, RFc or ciné. The RFc reveals and economically portrays the spread of excitability and suppression across the receptive field, culminating in the generation of a spike. RFcs for LGN neurons and for simple cells recorded in cat cortical areas 17 and 18 are presented and interpreted in terms of classic ON/OFF regions. The availability of temporal information permits the separation of an excitatory exit response, generated when a moving bright spot leaves an OFF region, from an excitatory entrance response occurring when a bright spot enters an ON region, because these responses occur at different times (exit responses earlier). Spike emission remains coupled to (cross-correlated with) stimulus events over time periods as long as 96 ms, implying that some stimulus drive or afferent visual input is delayed by as much as 96 ms more than other input. This is a striking instance of temporal dispersion in the visual system. In some cells, said to be "spatiotemporally inseparable", the delay (latency) varies systematically across the visual field; i.e., the place for optimal stimulation varies with the time prior to spike emission. In these cells, the RFc shows receptive field structures which move across the visual field over trajectories equal to approximately twice the total conventional RF width.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2003

Gap junctional connexins in the developing mouse cardiac conduction system.

Gap junctional channels which couple myocytes mediate conduction phenomena in the heart. These channels are dodecamers of transmembrane proteins belonging to the connexin family (Cx). Three Cxs, Cx43, -40 and -45, have been found to be expressed in cardiomyocytes. Each of them has a distinct spatiotemporal pattern of expression, which is regulated during development. In the adult mouse heart, Cx43 is expressed in all the working myocytes and most of the conductive myocytes; Cx45 is weakly expressed in all conductive myocytes, including those of the nodal tissues; Cx40 expression is restricted to the atria and ventricular conduction system. Analysis of mice with deletions of Cx genes has provided evidence that Cx43, -40 and -45, and consequently the gap junctional channels they form, are involved in both heart function and development. For example, Cx40 deficiency results in sinoatrial conduction impairments, a significant decrease of the conduction velocity in the atria, and a delay of the propagation of impulse in the His bundle. Transgenic mouse lines with modified Cx40 genes are now being used to draw up a detailed map of the conduction system in the adult and developing heart, and to identify the regulatory elements involved in the transcriptional regulation of the Cx40 gene. Some preliminary results of these studies are described.

Animals↗
PubMed2004

Understanding endothelin-1 function during craniofacial development in the mouse and zebrafish.

Morphogenesis of the face and neck is driven by an intricate relay of signaling molecules and transcription factors organized into hierarchical pathways. The coordinated action of these pathways regulates the development of neural crest cells within the pharyngeal arches, resulting in proper spatiotemporal formation of bone, cartilage, and connective tissue. While the functions of many genes involved in these processes were initially elucidated through the use of knockout technology in the mouse, increasing numbers of zebrafish craniofacial mutants have led to a rapid expansion in the identification of genes involved in craniofacial development. A comparative analysis of signaling pathways involved in these processes between mouse and zebrafish holds the potential not only to pinpoint conserved and therefore crucial gene functions in craniofacial development, but also to rapidly identify and study downstream effectors. These complementary approaches will also allow rapid identification of candidate genes and gene functions disrupted in human craniofacial dysmorphologies. In this brief review, we present a comparative analysis of one molecule involved in craniofacial development, endothelin-1, a small, secreted protein that is crucial for patterning the neural crest cells that give rise to lower jaw and throat structures.

Animals↗
PubMed2003

Cloning, expression and relationship of zebrafish gbx1 and gbx2 genes to Fgf signaling.

The organizer at the midbrain-hindbrain boundary (MHB) forms at the interface between Otx2 and Gbx2 expressing cell populations, but how these gene expression domains are set up and integrated with the remaining machinery controlling MHB development is unclear. Here we report the isolation, mapping, chromosomal synteny and spatiotemporal expression of gbx1 and gbx2 in zebrafish. We focus in particular on the expression of these genes during development of the midbrain-hindbrain territory. Our results suggest that these genes function in this area in a complex fashion, as evidenced by their highly dynamic expression patterns and relation to Fgf signaling. Analysis of gbx1 and gbx2 expression during formation of the MHB in mutant embryos for pax2.1, fgf8 and pou2 (noi, ace, spg), as well as Fgf-inhibition experiments, show that gbx1 acts upstream of these genes in MHB development. In contrast, gbx2 activation requires ace (fgf8) function, and in the hindbrain primordium, also spg (pou2). We propose that in zebrafish, gbx genes act repeatedly in MHB development, with gbx1 acting during the positioning period of the MHB at gastrula stages, and gbx2 functioning after initial formation of the MHB, from late gastrulation stages onwards. Transplantation studies furthermore reveal that at the gastrula stage, Fgf8 signals from the hindbrain primordium into the underlying mesendoderm. Apart from the general involvement of gbx genes in MHB development reported also in other vertebrates, these results emphasize that early MHB development can be divided into multiple steps with different genetic requirements with respect to gbx gene function and Fgf signaling. Moreover, our results provide an example for switching of a specific gene function of gbx1 versus gbx2 between orthologous genes in zebrafish and mammals.

Amino Acid Sequence↗
PubMed1984

Effects of disturbed sleep on contingent negative variation.

To understand better the pathophysiological aspects of disturbed sleep, six healthy male students underwent a series of sleep recordings. On the experimental night, subjects' sleep was disturbed, and the effects on contingent negative variation (CNV) were studied. Mean CNV amplitude decreased in magnitude in the Fz as well as Cz areas; the decrease in Fz-CNV tended to be greater in those subjects whose sleep was most disturbed. The decrease in amplitude of CNV appears to be a nonspecific phenomenon that occurs after any kind of disturbed sleep. Contingent negative variation is composed of two or more components with different spatiotemporal distribution. Depending on the placement of electrodes, the effect that disturbed sleep has on CNV will or will not be observed. The decreases in CNV amplitude were noted in the Fz and Cz areas. Other than subjective discomforts, psychometric measurements did not change significantly. Our data indicate, from the topographical and constructional analysis of CNVs, the possible involvement of the frontal lobe function after disturbed sleep.

Adult↗
PubMed1997

Pattern formation and spatiotemporal irregularity in a model for macrophage-tumour interactions.

Solid tumours do not develop as a homogeneous mass of mutant cells, rather, they grow in tandem with normal tissue cells initially present, and may also recruit other cell types including lymphatic and endothelial cells. Many solid tumours contain a high proportion of macrophages, a type of white blood cell which can have a variety of effects upon the tumour, leading to a delicate balance between growth promotion and inhibition. In this paper we present a brief review of the main properties and interactions of such tumour-associated macrophages, leading to a description of a mathematical model for the spatial interactions of macrophages, tumour cells and normal tissue cells, focusing on the ability of macrophages to kill mutant cells. Analysis of the homogeneous steady states shows that, for this model, normal tissue is unstable to the introduction of mutant cells despite such an immune response, but that the composition of the resulting tumour can be significantly altered. Including random cell movement and chemical diffusion, we demonstrate the existence of travelling wave solutions connecting the normal tissue and tumour steady states, corresponding to a growing tumour, and of the development of a spatial instability behind the wave front. Numerical solutions are illustrated in one and two dimensions. We go on to estimate macrophage motility parameters using data from Boyden chamber experiments. We then extend our model to include macrophage chemotaxis, that is, their directed movement in response to gradients of chemicals secreted by tumours. Solutions in one dimension indicate the possibility of spatiotemporal irregularities within the growing tumour, which are deduced to be the result of a series of bifurcations as the effective domain length increases, leading to a permanently transient solution. These results suggest that tumour heterogeneity may arise, in part, as a natural consequence of the macrophage infiltration. Recent experiments suggest that macrophages may indeed be involved in spatiotemporal variations within some human tumours.

Cell Movement↗
PubMed2026

Pervasive hybridization and introgression in Diervilleae (Caprifoliaceae).

Diervilleae (Caprifoliaceae) is a horticulturally important lineage with striking floral diversity and a long history of interspecific crossing, suggesting reticulate evolution. We integrated nuclear SNPs and whole plastome data to reconstruct a phylogenomic backbone for the tribe and to identify hybrids, cultivated accessions, and introgression among lineages. Nuclear and plastid phylogenies consistently recover Weigela and Diervilla as reciprocally monophyletic and resolve four major lineages within Weigela, providing a reproducible framework for revising sectional limits and species boundaries. Cultivated accessions form a well supported clade sister to W. florida and show predominantly W. florida ancestry while retaining contributions from multiple wild lineages, consistent with recurrent crossing, backcrossing, and selection. Analyses of wild populations reveal recurrent hybrids and enable plausible parental combinations to be inferred. Tests across the genome further indicate strong evidence for historical introgression across Diervilleae, with the strongest signals involving W. middendorffiana, W. maximowiczii, and Diervilla. Fossil evidence, divergence time estimation, and paleodistribution modelling together suggest range expansion during the Miocene and Pliocene followed by climate driven contraction, providing a spatiotemporal context for episodic contact, introgression, and the East Asia-North America disjunction.

Hybridization, Genetic↗
PubMed2001

Psychophysics of reading. XX. Linking letter recognition to reading speed in central and peripheral vision.

Our goal is to link spatial and temporal properties of letter recognition to reading speed for text viewed centrally or in peripheral vision. We propose that the size of the visual span - the number of letters recognizable in a glance - imposes a fundamental limit on reading speed, and that shrinkage of the visual span in peripheral vision accounts for slower peripheral reading. In Experiment 1, we estimated the size of the visual span in the lower visual field by measuring RSVP (rapid serial visual presentation) reading times as a function of word length. The size of the visual span decreased from at least 10 letters in central vision to 1.7 letters at 15 degrees eccentricity, in good agreement with the corresponding reduction of reading speed measured by Chung and coworkers (Chung, S. T. L., Mansfield, J. S., & Legge, G. E. (1998). Psychophysics of reading. XVIII. The effect of print size on reading speed in normal peripheral vision. Vision Research, 38, 2949-2962). In Exp. 2, we measured letter recognition for trigrams (random strings of three letters) as a function of their position on horizontal lines passing through fixation (central vision) or displaced downward into the lower visual field (5, 10 and 20 degrees ). We also varied trigram presentation time. We used these data to construct visual-span profiles of letter accuracy versus letter position. These profiles were used as input to a parameter-free model whose output was RSVP reading speed. A version of this model containing a simple lexical-matching rule accounted for RSVP reading speed in central vision. Failure of this version of the model in peripheral vision indicated that people rely more on lexical inference to support peripheral reading. We conclude that spatiotemporal characteristics of the visual span limit RSVP reading speed in central vision, and that shrinkage of the visual span results in slower reading in peripheral vision.

Analysis of Variance↗
PubMed2002

Tissue Doppler imaging for the assessment of left ventricular systolic and diastolic functions.

Doppler tissue imaging is a technique that allows recording of the low Doppler shift frequencies of high energy generated by the ventricular walls motion that are purposely filtered out in standard Doppler blood flow studies. Doppler tissue imaging can be performed with the use of pulsed Doppler, color two-dimensional Doppler, and color M-mode Doppler. Pulsed Doppler tissue imaging offers a high temporal resolution and therefore can be appropriately used for analysis of temporal relation between myocardium systolic and diastolic velocity waves. Color two-dimensional Doppler provides a good spatial resolution that permits differentiation of the velocity profiles between subendocardial and subepicardial layers but is limited by its poor temporal resolution. M-mode color-coded tissue imaging is characterized by a high spatiotemporal resolution, but sampling is only performed on a single line. Both two-dimensional and M-mode color-coded tissue imaging require specific modification of the current ultrasound machines. The present article reviews how Doppler tissue imaging may contribute to the noninvasive assessment of systolic and diastolic myocardial functions.

Animals↗
PubMed2006

Patterns of oral-nasal balance in normal speakers with and without cleft palate.

OBJECTIVE: The aero-acoustic aspects of nasalization that distinguish speakers with velopharyngeal adequacy from those with velopharyngeal inadequacy are well known. Differences in aerodynamic aspects of nasalization also have been demonstrated in normal speakers with cleft palate and their noncleft counterparts. The purpose of this study was to compare the amplitude and temporal patterns of oral-nasal balance in speakers with cleft palate and normal speech to those with normal speech without cleft palate. PATIENTS AND METHODS: Using the Nasal Accelerometric Vibrational Index technique, the time course and amplitude of oral-nasal balance were studied in 10 children with cleft palate and velopharyngeal adequacy and 10 noncleft controls. The speech sample included syllable, word, and sentence contexts, most of which were devoid of nasal consonants. RESULTS: The results indicate few differences between the two groups in contexts devoid of nasal consonants. However, significant differences were evident with regard to temporal aspects of oral-nasal balance in a nasal-oral consonant word context. CONCLUSIONS: Subtle structural-motor differences that may exist between normal speakers with and without cleft palate may be more evident when the spatiotemporal requirements for velar movement become more complex and result in a greater possible combination of oral-nasal impedance ratios.

Case-Control Studies↗