Publications by authors named "Nathan Holton"

Organisms with smaller genomes often perform multiple functions using one multi-subunit protein complex. The Silent Information Regulator complex (SIRc) carries out all of the core functions of heterochromatin. SIR complexes first drive the initiation and spreading of histone deacetylation in an iterative manner.

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The mechanisms that regulate post-natal growth of the craniofacial complex and that ultimately determine the size and shape of our faces are not well understood. Hippo signaling is a general mechanism to control tissue growth and organ size, and although it is known that Hippo signaling functions in neural crest specification and patterning during embryogenesis and before birth, its specific role in postnatal craniofacial growth remains elusive. We have identified the transcription factor FoxO6 as an activator of Hippo signaling regulating neonatal growth of the face.

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Introduction: Children with high body mass index (BMI) values have been demonstrated to have precocious dental development. Research has largely focused on cross-sectional data sets, leaving an incomplete understanding of the longitudinal relationship between BMI and dental maturation.

Methods: We used a pure longitudinal growth series to examine the relationship between dental development and childhood BMI.

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Objectives: The long-term skeletal effects of Class II treatment in growing individuals using high-pull facebow headgear and fixed edgewise appliances have not been reported. The purpose of this study was to evaluate the long-term skeletal effects of treatment using high-pull headgear followed by fixed orthodontic appliances compared to an untreated control group.

Materials And Methods: Changes in anteroposterior and vertical cephalometric measurements of 42 Class II subjects (n = 21, mean age = 10.

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Objectives: Assessing the strength of integration among different regions of the modern human nasal complex is important for developing a more thorough understanding of the determinants of nasal morphology. Given the morphogenetic influence of cartilage on adjacent intramembranous growth sites, the interaction between chondrocranial- versus intramembranous-derived nasal structures may have a significant influence on patterns of nasal variation. The purpose of this study is to examine integration between the chondrocranial- and intramembranous-derived regions of the nasal complex.

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Introduction: The aim of this in-vitro study was to evaluate the influence of cone-beam computed tomography scans on the diagnosis of chemically simulated external root resorption.

Methods: One hundred extracted anterior teeth were selected. Subsurface demineralization was induced on a limited area of the apical third of the root of 49 teeth.

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Gene trap mutagenesis is a powerful tool to create loss-of-function mutations in mice and other model organisms. Modifications of traditional gene trap cassettes, including addition of conditional features in the form of Flip-excision (FlEx) arrays to enable directional gene trap cassette inversions by Cre and Flpe site-specific recombinases, greatly enhanced their experimental potential. By taking advantage of these conditional gene trap cassettes, we developed a generic strategy for generating conditional mutations and validated this strategy in mice carrying a multipurpose allele of the transcription factor gene.

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Introduction: Genetic studies of malocclusion etiology have identified 4 deleterious mutations in genes DUSP6,ARHGAP21, FGF23, and ADAMTS1 in familial Class III cases. Although these variants may have large impacts on Class III phenotypic expression, their low frequency (<1%) makes them unlikely to explain most malocclusions. Thus, much of the genetic variation underlying the dentofacial phenotypic variation associated with malocclusion remains unknown.

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The nasal septal cartilage is thought to be a key growth center that contributes to nasofacial skeletal development. Despite the developmental influence of the nasal septum however, humans often exhibit a high frequency of septal deviation suggesting discordance in the growth between the septum and surrounding nasofacial skeleton. While there are numerous etiological factors that contribute to septal deviation, the surrounding nasofacial skeleton may also act to constrain the septum, resulting in altered patterns of growth.

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The zygomatic arch is morphologically complex, providing a key interface between the viscerocranium and neurocranium. It also serves as an attachment site for masticatory muscles, thereby linking it to the feeding apparatus. Though morphological variation related to differential loading is well known for many craniomandibular elements, the adaptive osteogenic response of the zygomatic arch remains to be investigated.

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Sox2 marks dental epithelial stem cells (DESCs) in both mammals and reptiles, and in this article we demonstrate several Sox2 transcriptional mechanisms that regulate dental stem cell fate and incisor growth. Conditional Sox2 deletion in the oral and dental epithelium results in severe craniofacial defects, including impaired dental stem cell proliferation, arrested incisor development and abnormal molar development. The murine incisor develops initially but is absorbed independently of apoptosis owing to a lack of progenitor cell proliferation and differentiation.

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Objectives: The curve of Spee (COS) is a mesio-distally curved alignment of the canine through distal molar cusp tips in certain mammals including modern humans and some fossil hominins. In humans, the alignment varies from concave to flat, and previous studies have suggested that this difference reflects craniofacial morphology, including the degree of alveolar prognathism. However, the relationship between prognathism and concavity of the COS has not been tested in craniofacially variant populations.

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While the nasal septum exerts a morphogenetic influence on the facial skeleton, there is evidence that this relationship is highly variable. To better appreciate the precise role of the septum, it is important understand the variable interaction between the septum and surrounding skeleton during ontogeny. Here we analyzed nasal septal and facial skeletal postnatal phenotypic variation using cross-sectional samples of C3H/HeJ and C57BL/6J mice.

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Objectives: Potential integration between the nasal region and noncranial components of the respiratory system has significant implications for understanding determinants of craniofacial variation. There is increasing evidence that sexual dimorphism in body size and associated male-female differences in energetically relevant variables influence the development of the nasal region. To better understand this relationship, we examined the ontogeny of sexual dimorphism in nasal shape using a longitudinal series of lateral cephalograms.

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During ontogeny, the nasal septum exerts a morphogenetic influence on the surrounding facial skeleton. While the influence of the septum is well established in long snouted animal models, its role in human facial growth is less clear. If the septum is a facial growth center in humans, we would predict that deviated septal growth would be associated with facial skeletal asymmetries.

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Article Synopsis
  • The study investigates how altered maxillary growth affects mandibular rotation, which is relevant for treating jaw alignment issues.
  • Ten domestic pigs had their maxillary growth changed through surgery, allowing researchers to analyze differences in mandibular shape using advanced techniques.
  • Results showed that changes in the maxilla significantly influenced mandibular shape, leading to greater anterior rotation and accompanying changes in the condylar region, which could impact future treatments for skeletal discrepancies.
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Researchers have hypothesized that nasal morphology, both in archaic Homo and in recent humans, is influenced by body mass and associated oxygen consumption demands required for tissue maintenance. Similarly, recent studies of the adult human nasal region have documented key differences in nasal form between males and females that are potentially linked to sexual dimorphism in body size, composition, and energetics. To better understand this potential developmental and functional dynamic, we first assessed sexual dimorphism in the nasal cavity in recent humans to determine when during ontogeny male-female differences in nasal cavity size appear.

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Variation in recent human mandibular form is often thought to reflect differences in masticatory behavior associated with variation in food preparation and subsistence strategies. Nevertheless, while mandibular variation in some human comparisons appear to reflect differences in functional loading, other comparisons indicate that this relationship is not universal. This suggests that morphological variation in the mandible is influenced by other factors that may obscure the effects of loading on mandibular form.

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To understand how variation in nasal architecture accommodates the need for effective conditioning of respired air, it is necessary to assess the morphological interaction between the nasal cavity and other aspects of the nasofacial skeleton. Previous studies indicate that the maxillary sinuses may play a key role in accommodating climatically induced nasal variation such that a decrease in nasal cavity volume is associated with a concomitant increase in maxillary sinus volume. However, due to conflicting results in previous studies, the precise interaction of the nasal cavity and maxillary sinuses, in humans, is unclear.

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As a component of the chondrocranium, the nasal septum influences the anteroposterior dimensions of the facial skeleton. The role of the septum as a facial growth center, however, has been studied primarily in long-snouted mammals, and its precise influence on human facial growth is not as well understood. Whereas the nasal septum may be important in the anterior growth of the human facial skeleton early in ontogeny, the high incidence of nasal septal deviation in humans suggests the septum's influence on human facial length is limited to the early phases of facial growth.

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Introduction: The cervical vertebrae maturation (CVM) method has been advocated as a predictor of peak mandibular growth. A careful review of the literature showed potential methodologic errors that might influence the high reported reproducibility of the CVM method, and we recently established that the reproducibility of the CVM method was poor when these potential errors were eliminated. The purpose of this study was to further investigate the reproducibility of the individual vertebral patterns.

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Introduction: During facial growth, the maxilla and mandible translate downward and forward. Although the forward displacement of the maxilla is less than that of the mandible, the interarch relationship of the teeth in the sagittal view during growth remains essentially unchanged. Interdigitation is thought to provide a compensatory (tooth movement) mechanism for maintaining the pattern of occlusion during growth: the maxillary teeth move anteriorly relative to the maxilla while the mandibular teeth move posteriorly relative to the basilar mandible.

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The influence of the chondrocranium in craniofacial development and its role in the reduction of facial size and projection in the genus Homo is incompletely understood. As one component of the chondrocranium, the nasal septum has been argued to play a significant role in human midfacial growth, particularly with respect to its interaction with the premaxilla during prenatal and early postnatal development. Thus, understanding the precise role of nasal septal growth on the facial skeleton is potentially informative with respect to the evolutionary change in craniofacial form.

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Facial size reduction and facial retraction are key features that distinguish modern humans from archaic Homo. In order to more fully understand the emergence of modern human craniofacial form, it is necessary to understand the underlying evolutionary basis for these defining characteristics. Although it is well established that the cranial base exerts considerable influence on the evolutionary and ontogenetic development of facial form, less emphasis has been placed on developmental factors intrinsic to the facial skeleton proper.

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