Retrotransposon insertions associated with risk of neurologic and psychiatric diseases.

Transposable elements (TEs) are active in neuronal cells raising the question whether TE insertions contribute to risk of neuropsychiatric disease. While genome-wide association studies (GWAS) serve as a tool to discover genetic loci associated with neuropsychiatric diseases, unfortunately GWAS do not directly detect structural variants such as TEs. To examine the role of TEs in psychiatric and neurologic disease, we evaluated 17,000 polymorphic TEs and find 76 are in linkage disequilibrium with disease haplotypes (P < 10-6 ) defined by GWAS. From these 76 polymorphic TEs, we identify potentially causal candidates based on having insertions in genomic regions of regulatory chromatin and on having associations with altered gene expression in brain tissues. We show that lead candidate insertions have regulatory effects on gene expression in human neural stem cells altering the activity of a minimal promoter. Taken together, we identify 10 polymorphic TE insertions that are potential candidates on par with other variants for having a causal role in neurologic and psychiatric disorders.

Evolution of Ty1 copy number control in yeast by horizontal transfer and recombination.

Transposable elements constitute a large fraction of most eukaryotic genomes. Insertion of mobile DNA sequences typically has deleterious effects on host fitness, and thus diverse mechanisms have evolved to control mobile element proliferation. Mobility of the Ty1 retrotransposon in Saccharomyces yeasts is regulated by copy number control (CNC) mediated by a self-encoded restriction factor derived from the Ty1 gag capsid gene that inhibits virus-like particle function. Here, we survey a panel of wild and human-associated strains of S. cerevisiae and S. paradoxus to investigate how genomic Ty1 content influences variation in Ty1 mobility. We observe high levels of mobility for a tester element with a gag sequence from the canonical Ty1 subfamily in permissive strains that either lack full-length Ty1 elements or only contain full-length copies of the Ty1' subfamily that have a divergent gag sequence. In contrast, low levels of canonical Ty1 mobility are observed in restrictive strains carrying full-length Ty1 elements containing a canonical gag sequence. Phylogenomic analysis of full-length Ty1 elements revealed that Ty1' is the ancestral subfamily present in wild strains of S. cerevisiae, and that canonical Ty1 in S. cerevisiae is a derived subfamily that acquired gag from S. paradoxus by horizontal transfer and recombination. Our results provide evidence that variation in the ability of S. cerevisiae and S. paradoxus strains to repress canonical Ty1 transposition via CNC is regulated by the genomic content of different Ty1 subfamilies, and that self-encoded forms of transposon control can spread across species boundaries by horizontal transfer.

Development of a maxillomandibular arch form based on the center of resistance of teeth using cone-beam computed tomography.

INTRODUCTION: Controlling transverse discrepancies is necessary to ensure stable and functional occlusion. Altered molar inclinations can camouflage the transverse relationship. The purpose of this research was to evaluate the maxillomandibular relationship of the center of resistance (CR) of the arch form created by the CR of teeth and compare these CR arch forms by their skeletal patterns. METHODS: Sixty patients with minor crowding and normal posterior overjet were divided into 3 groups according to ANB angle: skeletal Class I group had ANB angle between 0° and 4° (n = 20), skeletal Class II group had ANB angle >4° (n = 20), and skeletal Class III group had ANB angle <0° (n = 20). The 3-dimensional coordinates of the CR were estimated using cone-beam computed tomography images and projected on the CR occlusal plane to obtain the 2-dimensional coordinates. The CR arch forms were constructed and evaluated using Matlab (MathWorks, Natick, Mass). RESULTS: On comparing maxillomandibular CR arch form widths, the maxilla was significantly larger than the mandible of the canine and first premolar. The mandible was larger in the first molar of the skeletal Class III group. The maxillomandibular CR arch form width ratios were between 0.97 and 1.35. On comparing maxillomandibular CR arch form areas, the maxilla was significantly larger than the mandible in the anterior segment, and the mandible was larger in the posterior segment. The ratios were between 0.86 and 2.25. In between-group comparison, the skeletal Class III group showed significantly greater arch forms in the mandible. CONCLUSIONS: CR arch forms had significant maxillomandibular differences throughout the arch. The maxillomandibular ratios could be a reference for site-specific transverse discrepancy analysis.

Fully automated identification of cephalometric landmarks for upper airway assessment using cascaded convolutional neural networks.

OBJECTIVES: The aim of the study was to evaluate the accuracy of a cascaded two-stage convolutional neural network (CNN) model in detecting upper airway (UA) soft tissue landmarks in comparison with the skeletal landmarks on the lateral cephalometric images. MATERIALS AND METHODS: The dataset contained 600 lateral cephalograms of adult orthodontic patients, and the ground-truth positions of 16 landmarks (7 skeletal and 9 UA landmarks) were obtained from 500 learning dataset. We trained a UNet with EfficientNetB0 model through the region of interest-centred circular segmentation labelling process. Mean distance errors (MDEs, mm) of the CNN algorithm was compared with those from human examiners. Successful detection rates (SDRs, per cent) assessed within 1-4 mm precision ranges were compared between skeletal and UA landmarks. RESULTS: The proposed model achieved MDEs of 0.80 ± 0.55 mm for skeletal landmarks and 1.78 ± 1.21 mm for UA landmarks. The mean SDRs for UA landmarks were 72.22 per cent for 2 mm range, and 92.78 per cent for 4 mm range, contrasted with those for skeletal landmarks amounting to 93.43 and 98.71 per cent, respectively. As compared with mean interexaminer difference, however, this model showed higher detection accuracies for geometrically constructed UA landmarks on the nasopharynx (AD2 and Ss), while lower accuracies for anatomically located UA landmarks on the tongue (Td) and soft palate (Sb and St). CONCLUSION: The proposed CNN model suggests the availability of an automated cephalometric UA assessment to be integrated with dentoskeletal and facial analysis.

Miniplate-anchored maxillary protraction in adolescent patients with cleft lip and palate: A literature review of study design, type and protocol, and treatment outcomes.

OBJECTIVE: To review the study design, type, protocol, and treatment outcomes of miniplate-anchored maxillary protraction (MAMP) in adolescent patients with unilateral or bilateral cleft lip and palate. SETTING/SAMPLE POPULATION: Five retrospective and two prospective studies (n = 138 patients) were selected as per the inclusion criteria. MATERIALS AND METHODS: The study design, type, protocol of MAMP and the amount of skeletodental change were investigated. RESULTS: Two studies adopted type 1 (two miniplates at the infrazygomatic crest with a facemask), four studies adopted type 2 (four miniplates at the infrazygomatic crest and mandibular symphysis and use of intermaxillary elastics), and one study compared the two types. The mean start age was older than 10 years except one study. The mean duration was less than 1 year in two studies, between 1 and 2 years in three studies, and more than 2 years in two studies. The type 1 used 500 g/side for 12-14 h/d, and the type 2 used three increase methods (100, 200, 250 g/side; 75, 150, 250 g/side; 150, 200, and 250 g/side) for 24 h/d. The ranges of A point advancement were 0.5°-4.2° in ΔSNA and 1.7-5.6 mm in ΔA-vertical reference plane, respectively. The ranges of rotation of the palatal plane, occlusal plane, and mandibular plane were -1.5° to 2.0°, -2.0° to 2.0°, -1.5° to 3.2°, respectively. The increase of overjet was ranged from 2.3 to 5.8 mm. CONCLUSION: The MAMP therapy is effective for the correction of maxillary hypoplasia in adolescent cleft patients despite different types and protocols.

Palatal temporary skeletal anchorage devices (TSADs): What to know and how to do?

OBJECTIVES: Since palatal temporary skeletal anchorage devices (TSADs) have become important tools for orthodontic treatment, this narrative review was aimed to provide an updated and integrated guidelines for the clinical application of palatal TSADs. SETTING AND SAMPLE POPULATION: A narrative review article including researches on palatal TSADs in orthodontics related to anatomy, success rate and clinical application. MATERIALS AND METHODS: The anatomical characteristics, success rate and its consideration factors and clinical application of palatal TSADs based on the direction of tooth movement were evaluated. RESULTS: To improve the stability of TSADs, hard tissue factors such as bone depth, cortical bone thickness, bone density and soft tissue thickness were evaluated. Anatomically risky structures, including the nasopalatine foramen, canal and the greater palatine foramen, nerve, vessel need to be identified before placement. The success rate of palatal TSADs was greater than that of the buccal inter-radicular space. Palatal TSADs have been used for various purposes because they can control tooth movement in all directions and, three-dimensionally; their applications include the retraction of anterior teeth, protraction of posterior teeth, distalization, intrusion, expansion and constriction. They can be applied directly or indirectly to the lingual arch or transpalatal arch. Design modifications using splinted 2 miniscrews have been suggested. CONCLUSION: Palatal TSADs allow clinicians to perform minimally invasive and easy placement with good stability by understanding the anatomical characteristics of the palatal region, and they show good control over 3-dimensional tooth movements in various clinical cases.

Automatic Cephalometric Landmark Identification System Based on the Multi-Stage Convolutional Neural Networks with CBCT Combination Images.

This study was designed to develop and verify a fully automated cephalometry landmark identification system, based on multi-stage convolutional neural networks (CNNs) architecture, using a combination dataset. In this research, we trained and tested multi-stage CNNs with 430 lateral and 430 MIP lateral cephalograms synthesized by cone-beam computed tomography (CBCT) to make a combination dataset. Fifteen landmarks were manually and respectively identified by experienced examiner, at the preprocessing phase. The intra-examiner reliability was high (ICC = 0.99) in manual identification. The results of prediction of the system for average mean radial error (MRE) and standard deviation (SD) were 1.03 mm and 1.29 mm, respectively. In conclusion, different types of image data might be the one of factors that affect the prediction accuracy of a fully-automated landmark identification system, based on multi-stage CNNs.

Force Distribution of a Novel Core-Reinforced Multilayered Mandibular Advancement Device.

A mandibular advancement device (MAD) is a commonly used treatment modality for patients with mild-to-moderate obstructive sleep apnea. Although MADs have excellent therapeutic efficacy, dental side effects were observed with long-term use of MADs. The aim of this study was to analyze the force distribution on the entire dentition according to the materials and design of the MADs. Three types of MADs were applied: model 1 (single layer of polyethylene terephthalate glycol (PETG)), model 2 (double layer of PETG + thermoplastic polyurethane (TPU)), and model 3 (core-reinforced multilayer). In the maxilla, regardless of the model, the incisors showed the lowest force distribution. In most tooth positions, the force distribution was lower in models 2 and 3 than in model 1. In the mandible, the mandibular second molar showed a significantly lower force in all models. The mandibular incisors, canines, and molars showed the highest force values in model 1 and the lowest values in model 3. Depending on the material and design of the device, the biomechanical effect on the dentition varies, and the core-reinforced multilayered MAD can reduce the force delivered to the dentition more effectively than the conventional single- or double-layer devices.

Computerized Assessment of Occlusion and Muscle Activity during Use of a Multilayer Clear Retainer: A Preliminary Study.

The aim of this preliminary study was to evaluate the short-term changes of occlusal contacts and muscle activity after orthodontic treatment during the use of a multi-layer clear retainer. Evaluation was done with the T-scan and BioEMG systems. A total of 18 subjects were included, who were evaluated at three time intervals-T0 at debonding, T1 at one month after retainer delivery, and T2 at four months after retainer delivery. The T-scan and electromyography (EMG) data were recorded simultaneously. The T-scan system recorded the occlusion time, disclusion time and force distribution. The EMG waves were quantified by calculating the asymmetry index and activity index. The time variables changed but not significantly. Occlusal force decreased in the anterior dentition and increased in the posterior dentition during T0-T2. There was no clear evidence of a relationship between unbalanced occlusal forces and muscle activity. In most subjects, the temporalis anterior muscle was more dominant than the masseter muscle. From this preliminary computerized study, there were no significant changes in the state of the occlusion or muscle activity during the short-term retention period.

Evaluation of interradicular space, soft tissue, and hard tissue of the posterior palatal alveolar process for orthodontic mini-implant, using cone-beam computed tomography.

INTRODUCTION: To investigate the anatomy of the posterior palatal alveolar process, which is often used for placement of the orthodontic mini-implant (OMI), and to suggest simple guidelines for safe placement of OMI. METHODS: Cone-beam computed tomography (CBCT) scans of 60 patients (30 men, 30 women; age range, 18-39 years; average age, 25.8 years) was used to measure the palatal interradicular distance, the palatal bone thickness, and the palatal soft-tissue thickness. Measurements were performed on the area from the maxillary canine to the maxillary second molar based on the vertical distance apical from the cementoenamel junction. The CBCT data were analyzed by Bonferroni correction for multiple testing and the multivariable mixed linear model. RESULTS: The palatal interradicular distance was the widest between the second premolar and the first molar and the narrowest between the first and second premolars. The palatal bone thickness at interdental sites was the thickest between the first and second premolars and the thinnest between the first and second molars. The interdental palatal soft-tissue thickness from the canine to the second premolar was thicker than any other area. There were minor measurement differences between genders and positive correlations between vertical distance from the cementoenamel junction plane and all of the parameters. CONCLUSION: In this study, we evaluated the anatomy of the posterior palatal area using CBCT scans of adult patients. The data will provide guidelines to the clinicians before OMI placement in the posterior palatal alveolar process.

The Envelope of Segmental Movement and Airway Changes After Mandibular Anterior Subapical Osteotomy in Skeletal Class II Protrusion Patients.

INTRODUCTION: This study aimed to determine the envelope of anterior segmental movement and changes in the inferior pharyngeal airway space (IPAS) and position of the hyoid bone following mandibular anterior subapical osteotomy (ASO) under local anesthesia in skeletal Class II patients with protrusion. METHODS: The subjects were 33 skeletal Class II adult patients with lip protrusion. They were treated by extraction of 4 premolars and mandibular ASO under local anesthesia. Surgical movement of mandibular anterior segment and IPAS after surgery was evaluated by mandibular superimposition using lateral cephalograms between before and immediately after surgery. The depth of osteotomy and overlapping ratio were measured. RESULTS: The mean retraction of the mandibular incisor was 4.04 mm at the tip and 4.29 mm at the root apex. The mean vertical movement of the mandibular incisor was 3.33 mm intrusion at the tip and 3.42 mm at the root apex. The axis of the mandibular incisor did not change significantly. Patients with deep curve of Spee showed significantly more intrusion of incisors, whereas the incisor axis became more proclined. The IPAS became narrower, and the hyoid bone moved downward after surgery. The decreased IPAS was positively correlated with retraction of root apex and proclination of the mandibular incisors. CONCLUSION: To establish precise surgical treatment objectives, a balance between the amount of intrusion and changes in axis should be sought after considering anatomical limitations. Mandibular ASO should be performed with caution in skeletal Class II patients vulnerable to airway-related problems.

Retroviral-like determinants and functions required for dimerization of Ty1 retrotransposon RNA.

During replication of long terminal repeat (LTR)-retrotransposons, their proteins and genome (g) RNA assemble into virus-like particles (VLPs) that are not infectious but functionally related to retroviral virions. Both virions and VLPs contain gRNA in a dimeric form, but contrary to retroviruses, little is known about how gRNA dimerization and packaging occurs in LTR-retrotransposons. The LTR-retrotransposon Ty1 from Saccharomyces cerevisiae is an informative model for studying LTR-retrotransposon and retrovirus replication. Using structural, mutational and functional analyses, we explored dimerization of Ty1 genomic RNA. We provide direct evidence that interactions of self-complementary PAL1 and PAL2 palindromic sequences localized within the 5'UTR are essential for Ty1 gRNA dimer formation. Mutations disrupting PAL1-PAL2 complementarity restricted RNA dimerization in vitro and Ty1 mobility in vivo. Although dimer formation and mobility of these mutants was inhibited, our work suggests that Ty1 RNA can dimerize via alternative contact points. In contrast to previous studies, we cannot confirm a role for PAL3, tRNAiMet as well as recently proposed initial kissing-loop interactions in dimer formation. Our data also supports the critical role of Ty1 Gag in RNA dimerization. Mature Ty1 Gag binds in the proximity of sequences involved in RNA dimerization and tRNAiMet annealing, but the 5' pseudoknot in Ty1 RNA may constitute a preferred Gag-binding site. Taken together, these results expand our understanding of genome dimerization and packaging strategies utilized by LTR-retroelements.

In Vitro Osteogenic Differentiation and Antibacterial Potentials of Chalcone Derivatives.

Chalcone derivatives have been investigated as therapeutic agents for the anticancer, antioxidant, and anti-inflammatory fields. In this study, we have synthesized four different types of chalcone derivatives and demonstrated in vitro bioactivities. We divided these derivatives into two groups of chalcones on the basis of similar substituents on the aromatic rings, and we tested cell viability and proliferation potentials, which indicated that the methoxy substituent on the A ring could enhance cytotoxicity and antiproliferation potential depending on the chalcone concentration. We also investigated osteogenic differentiation of C2C12 cells by ALP staining, the early marker for osteogenesis, which demonstrated that the chalcones could not only induce activity of BMP-2 but also inhibit the activity of noggin, a BMP antagonist. In addition, chalcone bearing hydroxyl groups at the 2-, 4-, and 6-position on the A ring inhibited treptococcus mutans growth, a major causative agent of dental caries. Therefore, we concluded that the chalcone derivatives synthesized in this research can be good candidates for therapeutic agents promoting bone differentiation, with an expectation of inhibiting S. mutans, in dentistry.

Gummy Smile Correction Using Lingual Orthodontics and Augmented Corticotomy in Extremely Thin Alveolar Housing.

BACKGROUND: Tooth movement out of anatomic limitations was assisted by augmented corticotomy using deproteinized bovine bone mineral. METHODS: Lip protrusion can be reduced by premolar extraction followed by retraction of the anterior teeth. Surgical intervention is appropriate when the alveolar bone housing of the anterior region is insufficient for the tooth movement. In this patient, corticotomy in upper palatal area and anterior segmented osteotomy in the mandible were performed. Anatomic limitation to the retraction was expanded by xenograft. An antero-posterior lingual appliance was used to bodily retract the upper anterior teeth. The gummy smile was resolved by intrusion of upper entire arch using 2 mid-palatal temporary skeletal anchorage devices. RESULTS: New bone formation was observed on palatal side of upper anterior teeth. The teeth were moved into augmented area without fenestration or vitality loss. Lip protrusion was resolved, and the gummy smile was effectively improved. CONCLUSIONS: Orthodontic tooth movement beyond the limitation of the alveolar bone housing can be achieved with surgical assistance, which can be performed under local anesthesia. Without orthognathic surgery, the gummy smile can be reduced using an antero-posterior lingual retractor with mid-palatal skeletal anchorage.

Morphologic evaluation of dentoalveolar structures of mandibular anterior teeth during augmented corticotomy-assisted decompensation.

INTRODUCTION: Our aim in this study was to evaluate the effect of augmented corticotomy on the decompensation pattern of mandibular anterior teeth, alveolar bone, and surrounding periodontal tissues during presurgical orthodontic treatment. METHODS: Thirty skeletal Class III adult patients were divided into 2 groups according to the application of augmented corticotomy labial to the anterior mandibular roots: experimental group (with augmented corticotomy, n = 15) and control group (without augmented corticotomy, n = 15). Lateral cephalograms and cone-beam computed tomography images were taken before orthodontic treatment and before surgery. The measurements included the inclination and position of the mandibular incisors, labial alveolar bone area, vertical alveolar bone height, root length, and alveolar bone thickness at 3 levels surrounding the mandibular central incisors, lateral incisors, and canines. RESULTS: The mandibular incisors were significantly proclined in both groups (P <0.001); however, the labial movement of the incisor tip was greater in the experimental group (P <0.05). Significant vertical alveolar bone loss was observed only in the control group (P <0.001). The middle and lower alveolar thicknesses and labial alveolar bone area increased in the experimental group. In the control group, the upper and middle alveolar thicknesses and labial alveolar bone area decreased significantly. There were no significant differences in dentoalveolar changes between the 3 kinds of anterior teeth in each group, except for root length in the experimental group (P <0.05). CONCLUSIONS: Augmented corticotomy provided a favorable decompensation pattern of the mandibular incisors, preserving the periodontal structures surrounding the mandibular anterior teeth for skeletal Class III patients.

Stability of Modified Maxillomandibular Advancement Surgery in a Patient With Preadolescent Refractory Obstructive Sleep Apnea.

Maxillomandibular advancement (MMA) surgery can be considered a primary single-stage treatment for improving the quality of life in patients with preadolescent refractory obstructive sleep apnea (OSA). The aim of the present report was to evaluate the treatment efficacy and stability of modified MMA surgery in a growing patient with morbidly severe symptoms and medical complications. Using the follow-up results from the questionnaire, polysomnography, 2-dimensional cephalometry, and 3-dimensional cone-beam computed tomography measurements, the success of modified MMA surgery was assessed in terms of the postoperative improvements of functions and esthetics and postretentive stability of the improvements throughout the growth period. The present report provides some clinical recommendations when considering skeletal surgery in preadolescent patients with OSA: 1) the decision criteria of MMA surgery as definite treatment; 2) the proper surgical design for both maximum enlargement of the airway and esthetic improvement; and 3) the postoperative facial growth for long-term stability of airway function and skeletal improvement. With a systematic multidisciplinary approach, early surgical intervention can be used to treat OSA in children successfully and permanently.

Anterior Decompensation Using Segmental Osteotomy for Patients With Mandibular Asymmetry.

To obtain sufficient correction of facial asymmetry by orthognathic surgery, precise and sufficient dental decompensation during preoperative orthodontic treatment is needed. Facial asymmetry often includes complicated 3-dimensional dental compensation in the anterior alveolar region, which can limit the treatment options and lengthen the treatment time. As an alternative, anterior decompensation using segmental osteotomy (ADSO) with the patient under local anesthesia could be a reasonable approach, as it represents an effective, selective, and relatively safe method for correcting lower anterior disharmony during preoperative treatment. Furthermore, ADSO can quickly eliminate anterior compensation and move the teeth to their proper positions such that the basal bone supports them beyond the anatomic limits. Precise evaluation and diagnosis using data obtained from 3-dimensional computed tomography should be performed for accurate ADSO. The present report describes the versatile use of ADSO for 2 patients with different types of severe facial asymmetry. In the first case, ADSO was performed to correct the anterior dentoalveolar yaw and in the second, to change the vertical positioning and inclination of the anterior teeth. In both cases, sufficient elimination of anterior compensation using ADSO guaranteed successful improvement of the facial asymmetry and stabilization of occlusion after orthognathic surgery. The use of ADSO during preoperative treatment can quickly and effectively correct lower anterior disharmony and facilitate surgical correction of facial asymmetry.

Effect of low-level laser therapy on orthodontic tooth movement into bone-grafted alveolar defects.

INTRODUCTION: The objective of this study was to investigate the effect of low-level laser therapy (LLLT) on the rate of orthodontic tooth movement (OTM) into bone-grafted alveolar defects based on different healing states. METHODS: Ten male beagles were randomly allocated to 3 groups: group C, OTM alone as a control; group G, OTM into the grafted defects; group GL, OTM into the grafted defects with LLLT. The maxillary second premolars were protracted into the defects for 6 weeks, immediately (G-0 and GL-0) and at 2 weeks (G-2 and GL-2) after surgery. The defects were irradiated with a diode laser (dose, 4.5 J/cm(2)) every other day for 2 weeks. The rates of OTM and alveolar bone apposition, and maturational states of the defects were analyzed by histomorphometry, microcomputed tomography, and histology. RESULTS: The total amounts of OTM and new bone apposition rates were decreased by LLLT, with increased bone mineral density and trabecular maturation in the defects. Group GL-2 had the slowest movement with root resorption in relation to less woven bone in the hypermatured defect. CONCLUSIONS: LLLT significantly decreased the rate of OTM into the bone-grafted surgical defects by accelerating defect healing and maturation, particularly when the start of postoperative OTM was delayed.