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In open bite cases, a comprehensive diagnostic differentiation is crucial in determining the best corrective therapy. In non‐surgical open bite treatment, fixed appliances, either labial or lingual, are usually employed. With the addition of extra‐radicular screws, more sophisticated orthodontic movements may now be performed without the necessity for orthognathic surgery. Clear aligner therapy, on the contrary, has grown in popularity as a treatment option for more complex cases, such as open bite malocclusions. This article discusses three cases with an anterior open bite that were treated using various mechanics as dictated by the malocclusion. Case 1 was addressed wholly using clear aligner therapy, with careful consideration of attachment geometry and mechanics. Case 2 with clear aligner therapy, attachment geometry selection, and vertical elastics; and Case 3 with clear aligner therapy, attachments, and temporary anchorage devices. [ABSTRACT FROM AUTHOR]

Eukaryotic cells carry a vast amount of DNA packaged in their nucleus as chromatin. During cell division, it further condenses into individual Chromosomes. The basic unit of chromatin is nucleosome which comprises 200 bp of DNA wrapped around an octamer of positively charged histone proteins (2 molecules each H2A, H2B, H3, and H4), and one molecule of Histone H1. The octamer forms a cylinder around which DNA is wrapped (∼146 bp/octamer) and continues to the similar adjacent unit (∼60 bp of linker DNA), forming a string of nucleosomes. The H1 histone brings nucleosomes closer by binding with the linker DNA. These 10–11 nm thick threads further condense into 30 nm fibres, achieving a higher level of compaction by binding with nonhistone chromosomal proteins (e.g., topoisomerase II, condensins and cohesins) to form a scaffold through which the 30 nm fibre passes, forming loops. The average size of the loops is 600 nm, each accommodating approximately 60 kb of DNA. Whereas 85% of DNA is distributed in the loops, about 15% is associated with the scaffolds. The chromatin which is condensed even at interphase is 'heterochromatin'. Constitutive heterochromatin comprises tandem repeats of short DNA sequences and is generally devoid of genes, transcription and recombination. A potentially active part of the genome forms the 'euchromatin', which also has a differential distribution of DNA that shows up as mutually exclusive G- and R-bands rich in tissue-specific and housekeeping genes, highlighting a highly organised compaction of DNA in the chromatin. Compared to these bands, >100 kb long 'topologically associating domains' (TADs) have been identified at the genome level as the functional unit of chromatin. For its differential functional states, chromatin constantly undergoes condensation and decondensation, mediated by the post-translational modification of histones (e.g. acetylation, methylation of lysine) and the displacement of nucleosomes by an ATP-dependent complex of proteins (e.g. SWI/SNF). DNA methylation is another mode of chromatin modification that affects chromatin function. Thus, a highly dynamic system of chromatin organisation not only encapsulates a large amount of DNA in the nucleus but ensures differential gene function in an orderly fashion. [ABSTRACT FROM AUTHOR]

Purpose: The cut-out of the cephalomedullary nail is among the most common post-surgery complications for intertrochanteric fractures. As a risk predictor, a tip-apex distance (TAD) below 25 mm, observed from orthogonal fluoroscopic views, is recommended in the literature. This study aims to demonstrate that TAD < 25 mm is a mathematically insufficient risk definition and to complement the TAD upper bound with an appropriate lower bound, with the introduction of a novel distance parameter, TADX, based on the orthogonal projection of the nail tip on the central femoral midline. Method: Through a mathematical simulation software, all the possible points that lie inside the AP and lateral views of the proximal femoral hemisphere are utilized to create a 3D grid that is sorted into geometrically safe and risk-bearing regions. Extending this methodology, TAD < 25 mm, 10 mm < TAD < 25 mm, and the ideal tip position volumes are simulated. Finally, intersection volumes are created by a combination of different candidate lower TADX bounds and TAD < 25 mm upper bound to determine satisfactory TADX limits. Results: Simulation of TAD-bound zones exposed that TAD is only a mathematically suitable parameter for defining the upper boundary but not the lower boundary for the optimal region. However, using a TADX lower limit creates a 3D volume that is much closer to the optimal tip region volumetrically and can still be as quickly calculated from 2D AP and lateral views. Conclusions: According to the mathematical simulations, the use of a TADX lower bound of 9 mm for small, 7.5 mm for medium, and 7 mm for large femoral heads in conjunction with a TAD upper bound of 25 mm is suggested. [ABSTRACT FROM AUTHOR]

Abstract Topologically associating domains (TAD) are a key structure of the 3D mammalian genomes. However, the prevalence and dynamics of TAD-like domains in single cells remain elusive. Here we develop a new algorithm, named deTOKI, to decode TAD-like domains with single-cell Hi-C data. By non-negative matrix factorization, deTOKI seeks regions that insulate the genome into blocks with minimal chance of clustering. deTOKI outperforms competing tools and reliably identifies TAD-like domains in single cells. Finally, we find that TAD-like domains are not only prevalent, but also subject to tight regulation in single cells.

Abstract Background While some non-coding RNAs (ncRNAs) are assigned critical regulatory roles, most remain functionally uncharacterized. This presents a challenge whenever an interesting set of ncRNAs needs to be analyzed in a functional context. Transcripts located close-by on the genome are often regulated together. This genomic proximity on the sequence can hint at a functional association. Results We present a tool, NoRCE, that performs cis enrichment analysis for a given set of ncRNAs. Enrichment is carried out using the functional annotations of the coding genes located proximal to the input ncRNAs. Other biologically relevant information such as topologically associating domain (TAD) boundaries, co-expression patterns, and miRNA target prediction information can be incorporated to conduct a richer enrichment analysis. To this end, NoRCE includes several relevant datasets as part of its data repository, including cell-line specific TAD boundaries, functional gene sets, and expression data for coding & ncRNAs specific to cancer. Additionally, the users can utilize custom data files in their investigation. Enrichment results can be retrieved in a tabular format or visualized in several different ways. NoRCE is currently available for the following species: human, mouse, rat, zebrafish, fruit fly, worm, and yeast. Conclusions NoRCE is a platform-independent, user-friendly, comprehensive R package that can be used to gain insight into the functional importance of a list of ncRNAs of any type. The tool offers flexibility to conduct the users’ preferred set of analyses by designing their own pipeline of analysis. NoRCE is available in Bioconductor and https://github.com/guldenolgun/NoRCE .

Animal development depends on not only the linear genome sequence that embeds millions of cis-regulatory elements, but also the three-dimensional (3D) chromatin architecture that orchestrates the interplay between cis-regulatory elements and their target genes. Compared to our knowledge of the cis-regulatory sequences, the understanding of the 3D genome organization in human and other eukaryotes is still limited. Recent advances in technologies to map the 3D genome architecture have greatly accelerated the pace of discovery. Here, we review emerging concepts of chromatin organization in mammalian cells, discuss the dynamics of chromatin conformation during development, and highlight important roles for chromatin organization in cancer and other human diseases.

Abstract In open bite cases, a comprehensive diagnostic differentiation is crucial in determining the best corrective therapy. In non‐surgical open bite treatment, fixed appliances, either labial or lingual, are usually employed. With the addition of extra‐radicular screws, more sophisticated orthodontic movements may now be performed without the necessity for orthognathic surgery. Clear aligner therapy, on the contrary, has grown in popularity as a treatment option for more complex cases, such as open bite malocclusions. This article discusses three cases with an anterior open bite that were treated using various mechanics as dictated by the malocclusion. Case 1 was addressed wholly using clear aligner therapy, with careful consideration of attachment geometry and mechanics. Case 2 with clear aligner therapy, attachment geometry selection, and vertical elastics; and Case 3 with clear aligner therapy, attachments, and temporary anchorage devices.

Prostate cancer is one of the leading causes of cancer death and affects millions of men in the world. The American Cancer Society estimated about 34,500 deaths from prostate cancer in the United States in year 2022. The Androgen receptor (AR) signaling is a major pathway that sustains local and metastatic prostate tumor growth. Androgen-deprivation therapy (ADT) is the standard of care for metastatic prostate cancer patient and can suppress the tumor growth for a median of 2–3 years. Unfortunately, the malignancy inevitably progresses to castration-resistant prostate cancer (CRPC) which is more aggressive and no longer responsive to ADT. Surprisingly, for most of the CPRC patients, cancer growth still depends on androgen receptor signaling. Accumulating evidence suggests that CRPC cells have rewired their transcriptional program to retain AR signaling in the absence of androgens. Besides AR, other transcription factors also contribute to the resistance mechanism through multiple pathways including enhancing AR signaling pathway and activating other complementary signaling pathways for the favor of AR downstream genes expression. More recent studies have shown the role of transcription factors in reconfiguring chromatin 3D structure and regulating topologically associating domains (TADs). Pioneer factors, transcription factors and coactivators form liquid-liquid phase separation compartment that can modulate transcriptional events along with configuring TADs. The role of AR and other transcription factors on chromatin structure change and formation of condensate compartment in prostate cancer cells has only been recently investigated and appreciated. This review intends to provide an overview of transcription factors that contribute to AR signaling through activation of gene expression, governing 3D chromatin structure and establishing phase to phase separation. A more detailed understanding of the spatial role of transcription factors in CRPC might provide novel therapeutic targets for the treatment of CRPC.

Introduction: There has long been a desire to understand, describe, and model gene regulatory networks controlling numerous biologically meaningful processes like differentiation. Despite many notable improvements to models over the years, many models do not accurately capture subtle biological and chemical characteristics of the cell such as high-order chromatin domains of the chromosomes. Methods: Topologically Associated Domains (TAD) are one of these genomic regions that are enriched for contacts within themselves. Here we present TAD-aware Regulatory Network Construction or TReNCo, a memory-lean method utilizing epigenetic marks of enhancer and promoter activity, and gene expression to create context-specific transcription factor-gene regulatory networks. TReNCo utilizes common assays, ChIP-seq, RNA-seq, and TAD boundaries as a hard cutoff, instead of distance based, to efficiently create context-specific TF-gene regulatory networks. Results: We used TReNCo to define the enhancer landscape and identify transcription factors (TFs) that drive the cardiac development of the mouse. Conclusion: Our results show that we are able to build specialized adjacency regulatory network graphs containing biologically relevant connections and time dependent dynamics.

Abstract Background The three-dimensional spatial organization of the genome plays important roles in chromatin accessibility and gene expression in multiple biological processes and has been reported to be altered in response to environmental stress. However, the functional changes in spatial genome organization during environmental changes in crop plants are poorly understood. Results Here we perform Hi-C, ATAC-seq, and RNA-seq in two agronomically important rice cultivars, Nipponbare (Nip; Japonica) and 93-11 (Indica), to report a comprehensive profile of nuclear dynamics during heat stress (HS). We show that heat stress affects different levels of chromosome organization, including A/B compartment transition, increase in the size of topologically associated domains, and loss of short-range interactions. The chromatin architectural changes were associated with chromatin accessibility and gene expression changes. Comparative analysis revealed that 93-11 exhibited more dynamic gene expression and chromatin accessibility changes, including HS-related genes, consistent with observed higher HS tolerance in this cultivar. Conclusions Our data uncovered higher-order chromatin architecture as a new layer in understanding transcriptional regulation in response to heat stress in rice.

Tooth ankylosis is a disorder characterized by the fusion of tooth and alveolar bone. This case report describes the treatment of a severe open bite due to tooth ankylosis. A 14-year-old female patient with a chief complaint of masticatory dysfunction was diagnosed with skeletal Class III severe anterior open bite and tooth ankylosis. She visited our university hospital with a chief complaint of an anterior open bite. After the surgical luxation of the ankylosed maxillary right central incisor, the tooth was orthodontically retracted using a nickel-titanium wire. The right mandibular lateral incisor and canine were luxated and retracted using intermaxillary elastics from a temporary anchorage device (TAD), which was inserted in the opposite jaw. During the treatment, skeletal Class III malocclusion deteriorated due to anterior growth of the mandible. Therefore, TADs were inserted into the retromolar pad on both sides of the mandible and retracted into the mandibular dental arch. Although the mandibular right canine was luxated several times, it could not be brought to the occlusal line, and was thus extracted; the extraction space was replaced with a prosthesis. Consequently, a normal overjet and overbite with a straight profile were achieved. Extrusion of ankylosed teeth by intermaxillary elastics from a TAD is a valid treatment option for patients with severe open bites.

Copyright of Kieferorthopädie: die Zeitschrift für die Praxis is the property of Quintessenz Verlags GmbH and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

X-linked acrogigantism (X-LAG) is the most severe form of pituitary gigantism and is characterized by aggressive growth hormone (GH)-secreting pituitary tumors that occur in early childhood. X-LAG is associated with chromosome Xq26.3 duplications (the X-LAG locus typically includes VGLL1 , CD40LG , ARHGEF6 , RBMX , and GPR101) that lead to massive pituitary tumoral expression of GPR101 , a novel regulator of GH secretion. The mechanism by which the duplications lead to marked pituitary misexpression of GPR101 alone was previously unclear. Using Hi-C and 4C-seq, we characterized the normal chromatin structure at the X-LAG locus. We showed that GPR101 is located within a topologically associating domain (TAD) delineated by a tissue-invariant border that separates it from centromeric genes and regulatory sequences. Next, using 4C-seq with GPR101 , RBMX , and VGLL1 viewpoints, we showed that the duplications in multiple X-LAG-affected individuals led to ectopic interactions that crossed the invariant TAD border, indicating the existence of a similar and consistent mechanism of neo-TAD formation in X-LAG. We then identified several pituitary active cis- regulatory elements (CREs) within the neo-TAD and demonstrated in vitro that one of them significantly enhanced reporter gene expression. At the same time, we showed that the GPR101 promoter permits the incorporation of new regulatory information. Our results indicate that X-LAG is a TADopathy of the endocrine system in which Xq26.3 duplications disrupt the local chromatin architecture forming a neo-TAD. Rewiring GPR101 -enhancer interaction within the new regulatory unit is likely to cause the high levels of aberrant expression of GPR101 in pituitary tumors caused by X-LAG. [ABSTRACT FROM AUTHOR]

Background: A growing body of evidence has revealed that the mammalian genome is organized into hierarchical layers that are closely correlated with and may even be causally linked with variations in gene expression. Recent studies have characterized chromatin organization in various porcine tissues and cell types and compared them among species and during the early development of pigs. However, how chromatin organization differs among pig breeds is poorly understood. Results: In this study, we investigated the 3D genome organization and performed transcriptome characterization of two adipose depots (upper layer of backfat [ULB] and greater omentum [GOM]) in wild boars and Bama pigs; the latter is a typical indigenous pig in China. We found that over 95% of the A/B compartments and topologically associating domains (TADs) are stable between wild boars and Bama pigs. In contrast, more than 70% of promoter-enhancer interactions (PEIs) are dynamic and widespread, involving over a thousand genes. Alterations in chromatin structure are associated with changes in the expression of genes that are involved in widespread biological functions such as basic cellular functions, endocrine function, energy metabolism and the immune response. Approximately 95% and 97% of the genes associated with reorganized A/B compartments and PEIs in the two pig breeds differed between GOM and ULB, respectively. Conclusions: We reported 3D genome organization in adipose depots from different pig breeds. In a comparison of Bama pigs and wild boar, large-scale compartments and TADs were mostly conserved, while fine-scale PEIs were extensively reorganized. The chromatin architecture in these two pig breeds was reorganized in an adipose depot-specific manner. These results contribute to determining the regulatory mechanism of phenotypic differences between Bama pigs and wild boar. [ABSTRACT FROM AUTHOR]

Topologically associating domains (TADs) are the structural and functional units of the genome. However, the functions of protein-coding genes existing in the same or different TADs have not been fully investigated. We compared the functional similarities of protein-coding genes existing in the same TAD and between different TADs, and also in the same gap region (the region between two consecutive TADs) and between different gap regions. We found that the protein-coding genes from the same TAD or gap region are more likely to share similar protein functions, and this trend is more obvious with TADs than the gap regions. We further created two types of gene–gene spatial interaction networks: the first type is based on Hi-C contacts, whereas the second type is based on both Hi-C contacts and the relationship of being in the same TAD. A graph auto-encoder was applied to learn the network topology, reconstruct the two types of networks, and predict the functions of the central genes/nodes based on the functions of the neighboring genes/nodes. It was found that better performance was achieved with the second type of network. Furthermore, we detected long-range spatially-interactive regions based on Hi-C contacts and calculated the functional similarities of the gene pairs from these regions. [ABSTRACT FROM AUTHOR]

Abstract Background Three-dimensional chromatin loop structures connect regulatory elements to their target genes in regions known as anchors. In complex plant genomes, such as maize, it has been proposed that loops span heterochromatic regions marked by higher repeat content, but little is known on their spatial organization and genome-wide occurrence in relation to transcriptional activity. Results Here, ultra-deep Hi-C sequencing of maize B73 leaf tissue was combined with gene expression and open chromatin sequencing for chromatin loop discovery and correlation with hierarchical topologically-associating domains (TADs) and transcriptional activity. A majority of all anchors are shared between multiple loops from previous public maize high-resolution interactome datasets, suggesting a highly dynamic environment, with a conserved set of anchors involved in multiple interaction networks. Chromatin loop interiors are marked by higher repeat contents than the anchors flanking them. A small fraction of high-resolution interaction anchors, fully embedded in larger chromatin loops, co-locate with active genes and putative protein-binding sites. Combinatorial analyses indicate that all anchors studied here co-locate with at least 81.5% of expressed genes and 74% of open chromatin regions. Approximately 38% of all Hi-C chromatin loops are fully embedded within hierarchical TAD-like domains, while the remaining ones share anchors with domain boundaries or with distinct domains. Those various loop types exhibit specific patterns of overlap for open chromatin regions and expressed genes, but no apparent pattern of gene expression. In addition, up to 63% of all unique variants derived from a prior public maize eQTL dataset overlap with Hi-C loop anchors. Anchor annotation suggests that

Editing is a post-transcriptional process that changes the content of nucleic acids occurring on both DNA and RNA levels. Inosine at position 34 in tRNA is one such example, commonly produced via the deamination of A34, catalyzed by adenosine deaminase acting on tRNA (ADAT or Tad). The formation of inosine is essential for cell viability. The eukaryotic deaminases normally consist of the catalytic subunit Tad2 and the structural subunit Tad3, but the catalytic process is poorly understood. Despite the conservation of the (pseudo-) catalytic domains, the heterodimeric enzyme Tad2/3 also possesses additional domains that could exhibit novel functions. Here we present the structure of the N-terminal domain of the Schizosaccharomyces pombe Tad2/3 heterodimeric tRNA(A34) deaminase (N-SpTad2), which shares ~30% sequence identities with uridine-cytidine or pantothenate kinases, but lacks the predicted kinase functions. While biochemical assays indicated that the domain is not a nucleic-acid binder, it is able to significantly influence the A34-tRNA deamination activity of the holoenzyme. Through co-expression and purification analyses, we deduce that N-SpTad2 plays a role in mediating protein-protein contacts and enhancing the stability and solubility of SpTad2/3, without which the deaminase is not functional. Taken together, our structural and biochemical studies highlighted the importance of the additional domains to the intrinsic deaminase functions of heterodimeric Tad2/3 enzymes and promoted our understanding on this essential post-transcriptional tRNA modification.

Small cell lung cancer (SCLC) is an aggressive form of lung cancer that uniquely changes the chromosomal structure, although the basis of aberrant gene expression in SCLC remains largely unclear. Topologically associated domains (TADs) are structural and functional units of the human genome. Genetic and epigenetic alterations in the cancer genome can lead to the disruption of TAD boundaries and may cause gene dysregulation. To understand the potential regulatory role of this process in SCLC, we developed the TAD boundary alteration–related gene identification in tumors (TARGET) computational framework, which enables the systematic identification of candidate dysregulated genes associated with altered TAD boundaries. Using TARGET to compare gene expression profiles between SCLC and normal human lung fibroblast cell lines, we identified >100 genes in this category, of which 24 were further verified in samples from patients with SCLC using NanoString. The analysis revealed synergistic chromatin structure alteration at the A/B compartment and TAD boundary levels that underlies aberrant gene expression in SCLC. TARGET is a novel and powerful tool that can be used to explore the relationship of chromatin structure alteration to gene dysregulation related to SCLC tumorigenesis, progression, and prognosis.

Three-dimensional (3D) chromosome structures are closely related to various chromosomal functions, and deep analysis of the structures is crucial for the elucidation of the functions. In recent years, chromosome conformation capture (3C) techniques combined with next-generation sequencing analysis have been developed to comprehensively reveal 3D chromosome structures. Micro-C is one such method that can detect the structures at nucleosome resolution. In this chapter, I provide a basic method for Micro-C analysis. I present and discuss a series of data analyses ranging from mapping to basic downstream analyses, including loop detection., (© 2025. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

AimThe aim of this study was to measure the transfer accuracy of computer-aided design/computer-aided manufacturing (CAD/CAM) insertion guides using mini-implants. The target value is the virtual planned position (100%). It is also clinically mandatory to use sterilised surgical guides (autoclaved at 137°C). The results obtained using sterilised and non-sterilised insertion guides were compared. In addition, the actual position of the mini-implants, as implemented, was compared with the digitally planned positions.Materials and MethodsFollowing CAD/CAM planning and production of 60 insertion guides made from synthetic resins that had been previously tested for suitability, 120 mini-implants were inserted in pairs and in blocks of the bone of the substitute material. Half of the insertion guides were sterilised, while the other half were non-sterilised. Compared with the position of the mini-implants in the digital plans, deviations in the apical and coronal distances between the mini-implants and insertion depth, as well as the included angle of the mini-implants to one another and to the surface of the bone substitute material, were determined.ResultsIn post-sterilisation, the dimensional and material changes were observed. When compared, the deviations to the virtual planned position were achieved when the performed insertion using sterilised insertion guides were lower than those achieved when using non-sterilised insertion guides. The heat treatment during the sterilisation process improved the accuracy of the insertion guides. When comparing sterile insertion guides to the digital planned position (100%), the mean coronal deviation was 0.057 mm (0.81%), the apical deviation was 0.428 mm (6.11%), and insertion depth mean deviation at the right side was 0.15 mm (2.15%), while that on the left was 0.073 mm (1.04%).ConclusionThe CAD/CAM TAD insertion guide could not achieve 100% accuracy in translating the digitally planned position into the real anatomic location. Deviations to the ideal position between 0.81 and 6.11% were observed. Clinically, for appliances that fit post-mini-implant insertion, the coronal distance of the mid-mini-implant head is the most important. At this point, the mean deviation to the planned positions is 0.81%, which is clinically acceptable and most likely reproducible by using CAD/CAM insertion guides.

Featured Application: This study examined the dynamics of the dentition when the dentition was moved backward with TAD using photoelasticity. The objective of this study was to determine whether the distribution of compressional and tensional stress around tooth roots is influenced by the position of a temporary anchorage device and the length of the retraction hook during the distalization of the maxillary dentition. A photoelastic orthodontic model was made of photoelastic epoxy resin. Six combinations of three retraction hook lengths and two posterior Temporary skeletal anchorage devices (TAD) positions were established. Stress was applied through an elastic chain for each of the combinations. Digital photoelastic stress analysis measured the compression, tensional stress, and direction around the tooth root. Using this novel photoelastic model, we found that the distribution of compressional and tensional stress during the retraction of the maxillary dentition was significantly influenced by the position of the TAD and the length of the retraction hook. [ABSTRACT FROM AUTHOR]

Introduction: Tip-apex-distance (TAD) has been widely advocated as the index to predict the risk of screw cut out in hip fractures treated with sliding hip screw devices. The fluoroscopic extents of the femoral head can change with the slightest change in the limb position which includes internal and external rotations, adduction and abduction. These changes can affect the visible TAD and articular-clearance of the screw-tip. The purpose of this Computed-tomography(CT) based analysis is to analyze the variations of the radiographically visible articular-clearance and TAD measurements with limb positioning and to determine the appropriate fluoroscopic projections for different screw-positions within the femoral head.Material and Methods: We retrospectively analysed CT studies of twenty healthy proximal femora. Spatial markers simulating screw tips were placed in the different combinations of anteroposterior(AP) and cephalocaudal(CC) positions. Software-based AP and lateral radiographs were developed for each screw position. Additional AP radiographs with femur in internal and external rotation, and lateral radiographs with the femur in adduction and abduction were developed. The variation of TAD and articular-clearance of the screw was measured among these radiographs for individual screw tip positions.Results: Screw tip placed centrally in AP and CC planes position didn't show any significant variation in TAD and articular-clearance with modified AP and lateral radiographs. Significant differences were observed in TAD and articular-clearance values for other screw tip positions. Anteriorly placed screw tips had higher TAD and articular-clearance values with external rotation and similar changes were observed with posteriorly placed tips in internal rotation. Inferiorly placed tips had higher articular-clearance and TAD with limb abduction and similar changes were observed for superiorly placed tips with limb adduction.Conclusions: For the sliding screws placed in non-central locations, the clearance of the screw tip from the articular margins can not be appropriately estimated with conventional AP and lateral views. Additional views with the limb in internal rotation and external rotation in AP view, and adduction-abduction in lateral view are required to safely place the sliding screw in the femoral head. The limb should be brought to a neutral alignment for the accurate estimation of TAD. [ABSTRACT FROM AUTHOR]

For decades, biochemical methods for the analysis of genome structure and function provided cell-population-averaged data that allowed general principles and tendencies to be disclosed. Microscopy-based studies, which immanently involve single-cell analysis, did not provide sufficient spatial resolution to investigate the particularly small details of 3D genome folding. Nevertheless, these studies demonstrated that mutual positions of chromosome territories within cell nuclei and individual genomic loci within chromosomal territories can vary significantly in individual cells. The development of new technologies in biochemistry and the advent of super-resolution microscopy in the last decade have made possible the full-scale study of 3D genome organization in individual cells. Maps of the 3D genome build based on C-data and super-resolution microscopy are highly consistent and, therefore, biologically relevant. The internal structures of individual chromosomes, loci, and topologically associating domains (TADs) are resolved as well as cell-cycle dynamics. 3D modeling allows one to investigate the physical mechanisms underlying genome folding. Finally, joint profiling of genome topology and epigenetic features will allow 3D genomics to handle complex cell-to-cell heterogeneity. In this review, we summarize the present state of studies into 3D genome organization in individual cells, analyze the technical problems of single-cell studies, and outline perspectives of 3D genomics. • C-based technologies and super-resolution microscopy provide consistent and complementary data on the individual 3D genomes. • Sparse single-cell Hi-C maps require sophisticated technical controls prior to the analysis of biological features. • 3D genome displays cell-to-cell variability generated by stochastic fluctuations and dynamic specific interactions. • Joint profiling of epigenome and 3D genome in the same cell and live-cell imaging are perspective trends the in 3D genomics. [ABSTRACT FROM AUTHOR]

Introduction: Determination of difference between conventional and passive self-ligating brackets (SLBs) in respect of extraction space closure, patient perception and root resorption.Material and Methods: Eighty patients were divided into four groups of 20 each with age-sex-matched control using a simple randomisation technique and allocation concealment with a closed opaque envelope method. Group 1 consisted of conventional brackets with Connecticut New Archwire (CNA) wire mushroom loop, group 2 consisted of conventional brackets with TAD (AbsoAnchor, Korea) supported retraction, group 3 consisted of passive SLB with CNA archwires (Libral Traders, India) mushroom loop and group 4 consisted of passive SLB brackets with TAD (AbsoAnchor, Korea) supported retraction. The rate of retraction, root resorption and patient satisfaction were assessed. All conventional brackets (Orthox, USA) and passive SLBs (CaptainOrtho, India) had 0.018 Roth prescriptions with a slot size of 0.018 × 0.025.Results: Retraction was the fastest in group 2 with a mean of 1.266 ± 0.14 mm/4 week and a duration of 23.40 weeks. Similarly, group 4 showed the most sluggish movement with a mean of 1.182 ± 0.80 mm/4 weeks with a total duration of 25 weeks; howeverdifferencesce among groups were not statistically significant (P = 0.470).Conclusion: SLBs have advantage of better patient comfort, less pain and reduced chairside time. Though the present study found increased treatment duration with SLB along with friction mechanics, refuting the previous claims of reduced friction with SLBs, however, the difference was not statistically significant and results have to be extrapolated with caution and experience considering other advantages of SLBs. [ABSTRACT FROM AUTHOR]

Copyright of Kieferorthopädie: die Zeitschrift für die Praxis is the property of Quintessenz Verlags GmbH and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Latest advancements in genomics involving individuals from different races and geographical locations has led to the identification of thousands of common as well as rare genetic variants and copy number variations (CNVs). These studies have surprisingly revealed that the majority of genetic variation is not present within the coding region but rather in the non-coding region of the genome, which is also termed as “Medical Genome”. This short review describes how mutations/variations within; regulatory sequences, architectural proteins and transcriptional regulators give rise to the aberrant gene expression profiles that drives cellular transformations and malignancies.

Abstract Background Three-dimensional spatial organization of chromosomes is defined by highly self-interacting regions 0.1–1 Mb in size termed Topological Associating Domains (TADs). Genetic factors that explain dynamic variation in TAD structure are not understood. We hypothesize that common structural variation (SV) in the human population can disrupt regulatory sequences and thereby influence TAD formation. To determine the effects of SVs on 3D chromatin organization, we performed chromosome conformation capture sequencing (Hi-C) of lymphoblastoid cell lines from 19 subjects for which SVs had been previously characterized in the 1000 genomes project. We tested the effects of common deletion polymorphisms on TAD structure by linear regression analysis of nearby quantitative chromatin interactions (contacts) within 240 kb of the deletion, and we specifically tested the hypothesis that deletions at TAD boundaries (TBs) could result in large-scale alterations in chromatin conformation. Results Large (> 10 kb) deletions had significant effects on long-range chromatin interactions. Deletions were associated with increased contacts that span the deleted region and this effect was driven by large deletions that were not located within a TAD boundary (nonTB). Some deletions at TBs, including a 80 kb deletion of the genes CFHR1 and CFHR3, had detectable effects on chromatin contacts. However for TB deletions overall, we did not detect a pattern of effects that was consistent in magnitude or direction. Large inversions in the population had a distinguishable signature characterized by a rearrangement of contacts that span its breakpoints. Conclusions Our study demonstrates that common SVs in the population impact long-range chromatin structure, and deletions and inversions have distinct signatures. However, the effects that we observe are subtle and variable between loci. Genome-wide analysis of chromatin conformation in large cohorts will be needed to quantify the influence of common SVs on chromatin structure.

Introduction Orthodontic treatment of Class II Division 1 (II/1) malocclusions in adults can be challenging since skeletal effects are limited. Possible treatment options are orthodontic camouflage or orthognatic surgery, in severe cases. The aim of this paper was to present a successful management of Class II malocclusion in an adult patient using temporary anchorage devices (TADs). Case report After detailed clinical examination, study models and cephalometric analysis, a 26 years old patient was diagnosed with Class II malocclusion, an overjet of 12 mm, congenitally missing tooth 41 and midline shifted to the right in upper dental arch. In prior orthodontic treatment, patient had upper premolars extracted. Posterior teeth in upper left quadrant were shifted mesially. The camouflage treatment was considered, using temporary anchorage devices (TADs) to distalize posterior teeth on the left side, and gain space for incisor retraction and midline correction in upper dental arch. Results Using TADs as additional anchorage in anterior region and coil spring for molar distalization, the space was made for tooth 23, midline correction and incisor retraction. After 40 months, a satisfactory result was achieved, overjet and midline correction, class I canines occlusion and class II molar occlusion. Conclusion Class II/1 malocclusion in adults can be successfully treated using TADs. The success depends on the severity of malocclusion and patient cooperation.

Abstract Background Our understanding of the nuclear chromatin structure has increased hugely during the last years mainly as a consequence of the advances in chromatin conformation capture methods like Hi-C. The unprecedented resolution of genome-wide interaction maps shows functional consequences that extend the initial thought of an efficient DNA packaging mechanism: gene regulation, DNA repair, chromosomal translocations and evolutionary rearrangements seem to be only the peak of the iceberg. One key concept emerging from this research is the topologically associating domains (TADs) whose functional role in gene regulation and their association with disease is not fully untangled. Results We report that the lower the number of protein coding genes inside TADs, the higher the tendency of those genes to be associated with disease (p-value = 4 × $$10^{-54}$$ 10-54 ). Moreover, housekeeping genes are less associated with disease than other genes. Accordingly, they are depleted in TADs containing less than three protein coding genes (p-value = 3.9 × $$10^{-34}$$ 10-34 ). We observed that TADs with higher ratios of enhancers versus genes contained higher numbers of disease-associated genes. We interpret these results as an indication that sharing enhancers among genes reduces their involvement in disease. Larger TADs would have more chances to accommodate many genes and select for enhancer sharing along evolution. Conclusions Genes associated with human disease do not distribute randomly over the TADs. Our observations suggest general rules that confer functional stability to TADs, adding more evidence to the role of TADs as regulatory units.

Introduction: Temporary Anchorage Devices have revolutionized our approach to anchorage management. However, their placement may carry risks, such as root perforation, damage to the periodontal ligament, buccal-nasal communication, etc. The aim of this article is to describe an original protocol in two times for the placement of a palatal mini-screw through guided surgery using a guide created by Computer-Aided Design and Manufacturing (CAD/CAM) followed by the transfer of placement information to the laboratory for the fabrication of a Custom Medical Device (CMD) for distalization., Materials and Methods: A two-stage protocol is described and illustrated step by step. Phase 1 comprises 7 steps (including superimposition of maxillary cast and profile teleradiography, surgical tray design), followed by phase 2, which involves 3 final steps (including production of impression for laboratory, production of laboratory model with transfer of mini-screw position)., Results: Although the position of the mini screws remains precise, a discrepancy between the planning and the intraoral situation exists. The addition of a second step therefore enables the distalization appliance to be fitted precisely and without pitfalls. Finally, this protocol ensures safe placement, making work easier for the practitioner and, ultimately, for the patient., Conclusion: In a two-stage process, the placement of palatal mini screws through guided surgery using a guide created by CAD/CAM followed by the transfer of this information to the laboratory for the fabrication of a CMD for distalization proves to be a relevant approach.

Genome organization can regulate gene expression and promote cell fate transitions. The differentiation of germline stem cells (GSCs) to oocytes in Drosophila involves changes in genome organization mediated by heterochromatin and the nuclear pore complex (NPC). Heterochromatin represses germ cell genes during differentiation, and NPCs anchor these silenced genes to the nuclear periphery, maintaining silencing to allow for oocyte development. Surprisingly, we found that genome organization also contributes to NPC formation, mediated by the transcription factor Stonewall (Stwl). As GSCs differentiate, Stwl accumulates at boundaries between silenced and active gene compartments. Stwl at these boundaries plays a pivotal role in transitioning germ cell genes into a silenced state and activating a group of oocyte genes and nucleoporins (Nups). The upregulation of these Nups during differentiation is crucial for NPC formation and further genome organization. Thus, cross-talk between genome architecture and NPCs is essential for successful cell fate transitions., (© 2024 Kotb et al.; Published by Cold Spring Harbor Laboratory Press.)

Background: The intertrochanteric fracture is a frequently occurring fracture, often attributed to osteoporosis in older populations. Recently, there has been a proposal to perform early surgical fixation on elderly patients to facilitate early rehabilitation. This approach has been shown to have a beneficial effect in lowering comorbidities. The study aims to compare the efficacy of the twin screw derotation type cephalomedullary nail with that of the single helical blade type cephalomedullary nail in the management of unstable intertrochanteric fractures., Methodology:  The research sample included patients from the orthopedic outpatient and emergency departments of Adesh Medical College and Hospital, Ambala Cantt, India, who were scheduled for surgery for unstable intertrochanteric femur fractures. The patients were categorized into two groups according to the kind of implant they were given: either a twin screw derotation cephalomedullary nail or a single helical blade cephalomedullary nail. The functional result was evaluated by comparing the modified Harris hip score (HHS). Patients with unstable intertrochanteric fractures, including reverse oblique fractures and fractures with posteromedial comminution, as well as patients who provided consent, were included in this study., Results:  Thirteen individuals received treatment with proximal femoral nail antirotation (PFNA2), whereas 19 individuals received treatment with proximal femoral nail (PFN). The mean age in the PFNA2 group was 69.51, whereas the mean age in the PFN group was 70.804. There were three patients in the PFNA2 group and five patients in the PFN group who had a tip apex distance of more than 25 mm. According to the Cleveland index, nine patients in the PFNA2 group and eight patients in the PFN group had an implant location that was not optimum. Four patients in the PFNA2 group and seven patients in the PFN group had a neck shaft angle difference of more than 10° between their undamaged and operated sides. The mean HHS was 74.55 for the PFNA2 group and 69.88 for the PFN group. The PFNA2 group exhibited four problems, whereas the PFN group had five issues., Conclusion:  The study found that both implants offer similar functional outcomes, with adherence to specific radiological parameters optimizing results. While both face similar challenges with osteoporosis, there was no notable distinction between them. Notably, the PFNA2 group showed superior outcomes in perioperative morbidity., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. The Central Ethical Committee of Adesh Medical College and Hospital, Ambala Cantt issued approval RES/AMC/RAD/2024-5. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Thusoo et al.)

Documentation of patient records helps to evaluate, plan, and monitor the treatment progress. It should be recorded timely and legibly. Recently, TADs are being used commonly in our orthodontic practice, but the precise description of the site requires lengthy cumbersome statements. Here, we describe an easy method to describe the TAD site, thus improving the efficiency of documentation. [ABSTRACT FROM AUTHOR]

Sex determination is the process by which an initial bipotential gonad adopts either a testicular or ovarian cell fate. The inability to properly complete this process leads to a group of developmental disorders classified as disorders of sex development (DSD). To date, dozens of genes were shown to play roles in mammalian sex determination, and mutations in these genes can cause DSD in humans or gonadal sex reversal/dysfunction in mice. However, exome sequencing currently provides genetic diagnosis for only less than half of DSD patients. This points towards a major role for the non-coding genome during sex determination. In this review, we highlight recent advances in our understanding of non-coding, cis-acting gene regulatory elements and discuss how they may control transcriptional programmes that underpin sex determination in the context of the 3-dimensional folding of chromatin. As a paradigm, we focus on the Sox9 gene, a prominent pro-male factor and one of the most extensively studied genes in gonadal cell fate determination. [ABSTRACT FROM AUTHOR]

Structural variations (SVs) are recognized to have an important role in transcriptional regulation, especially in the light of resolved 3D genome structure using high-throughput chromosome conformation capture (Hi-C) technology in mammals. However, the effect of SVs on 3D genome organization in plants remains rarely understood. In this study, we identified 295,496 SVs and 5251 topologically associating domains (TADs) in two diploid and two tetraploid cottons. We observed that approximately 16% of SVs occurred in TAD boundary regions that were called boundary affecting-structural variations (BA-SVs), and had a large effect on disrupting TAD organization. Nevertheless, SVs preferred occurring in TAD interior instead of TAD boundary, probably associated with the relaxed evolutionary selection pressure. We noticed the biased evolution of the At and Dt subgenomes of tetraploid cottons, in terms of SV-mediated disruption of 3D genome structure relative to diploids. In addition, we provide evidence showing that both SVs and TAD disruption could lead to expression difference of orthologous genes. This study advances our understanding of the effect of SVs on 3D genome organization and gene expression regulation in plants. • 295,496 SVs and 5251 TADs were identified in two diploid and two tetraploid cottons. • BA-SVs accounting for 16% of all SVs had a large effect on disrupting TAD organization. • SVs preferred occurring in TAD interior instead of TAD boundary. • Both SVs and TAD disruption could lead to expression difference of orthologous genes. [ABSTRACT FROM AUTHOR]

Skeletal muscle development and intramuscular fat (IMF) content, which positively contribute to meat production and quality, are regulated by precisely orchestrated processes. However, changes in three-dimensional chromatin structure and interaction, a newly emerged mediator of gene expression, during the skeletal muscle development and IMF deposition have remained unclear. In the present study, we analyzed the differences in muscle development and IMF content between one-day-old commercial Arbor Acres broiler (AA) and Chinese indigenous Lushi blue-shelled-egg chicken (LS) and performed Hi-C analysis on their breast muscles. Our results indicated that significantly higher IMF content, however remarkably lower muscle fiber diameter was detected in breast muscle of LS chicken compared to that of AA broiler. The chromatin intra-interaction was prior to inter-interaction in both AA and LS chicken, and chromatin inter-interaction was heavily focused on the small and gene-rich chromosomes. For genomic compartmentalization, no significant difference in the number of B type compartments was found, but AA had more A type compartments versus LS. The A/B compartment switching of AA versus LS showed more A to B switching than B to A switching. There were no significant differences in the average sizes and distributions of topologically associating domains (TAD). Additionally, approximately 50% of TAD boundaries were overlapping. The reforming and disappearing events of TAD boundaries were identified between AA and LS chicken breast muscles. Among these, the HMGCR gene was located in the TAD-boundary regions in AA broilers, but in TAD-interior regions in LS chickens, and the IGF2BP3 gene was located in the AA-unique TAD boundaries. Both HMGCR and IGF2BP3 genes exhibited increased mRNA expression in one-day-old AA broiler breast muscles. It was demonstrated that the IGF2BP3 and HMGCR genes regulated by TAD boundary sliding were potential biomarkers for chicken breast muscle development and IMF deposition. Our data not only provide a valuable understanding of higher-order chromatin dynamics during muscle development and lipid accumulation but also reveal new insights into the regulatory mechanisms of muscle development and IMF deposition in chicken.

Chromatin domains and loops are important elements of chromatin structure and dynamics, but much remains to be learned about their exact biological role and nature. Topological associated domains and functional loops are key to gene expression and hold the answer to many questions regarding developmental decisions and diseases. Here, we discuss new findings, which have linked chromatin conformation with development, differentiation and diseases and hypothesized on various models while integrating all recent findings on how chromatin architecture affects gene expression during development, evolution and disease.

Animal genomes are organized into topologically associated domains (TADs). TADs are thought to contribute to gene regulation by facilitating enhancer-promoter (E-P) contacts within a TAD and preventing these contacts across TAD borders. However, the absolute difference in contact frequency across TAD boundaries is usually less than 2-fold, even though disruptions of TAD borders can change gene expression by 10-fold. Existing models fail to explain this hypersensitive response. Here, we propose a futile cycle model of enhancer-mediated regulation that can exhibit hypersensitivity through bistability and hysteresis. Consistent with recent experiments, this regulation does not exhibit strong correlation between E-P contact and promoter activity, even though regulation occurs through contact. Through mathematical analysis and stochastic simulation, we show that this system can create an illusion of E-P biochemical specificity and explain the importance of weak TAD boundaries. It also offers a mechanism to reconcile apparently contradictory results from recent global TAD disruption with local TAD boundary deletion experiments. Together, these analyses advance our understanding of cis-regulatory contacts in controlling gene expression and suggest new experimental directions.

Background: While some non-coding RNAs (ncRNAs) are assigned critical regulatory roles, most remain functionally uncharacterized. This presents a challenge whenever an interesting set of ncRNAs needs to be analyzed in a functional context. Transcripts located close-by on the genome are often regulated together. This genomic proximity on the sequence can hint at a functional association. Results: We present a tool, NoRCE, that performs cis enrichment analysis for a given set of ncRNAs. Enrichment is carried out using the functional annotations of the coding genes located proximal to the input ncRNAs. Other biologically relevant information such as topologically associating domain (TAD) boundaries, co-expression patterns, and miRNA target prediction information can be incorporated to conduct a richer enrichment analysis. To this end, NoRCE includes several relevant datasets as part of its data repository, including cell-line specific TAD boundaries, functional gene sets, and expression data for coding & ncRNAs specific to cancer. Additionally, the users can utilize custom data files in their investigation. Enrichment results can be retrieved in a tabular format or visualized in several different ways. NoRCE is currently available for the following species: human, mouse, rat, zebrafish, fruit fly, worm, and yeast. Conclusions: NoRCE is a platform-independent, user-friendly, comprehensive R package that can be used to gain insight into the functional importance of a list of ncRNAs of any type. The tool offers flexibility to conduct the users' preferred set of analyses by designing their own pipeline of analysis. NoRCE is available in Bioconductor and https://github.com/guldenolgun/NoRCE. [ABSTRACT FROM AUTHOR]

The human β-globin locus control region (LCR) hypersensitive site 2 (HS2) is one of enhancers for transcription of the β-like globin genes in erythroid cells. Our previous study showed that the LCR HS2 has active chromatin structure before transcriptional induction of the β-globin gene, while another enhancer LCR HS3 is activated by the induction. To compare functional difference between them, we deleted each HS (ΔHS2 and ΔHS3) from the human β-globin locus in hybrid MEL/ch11 cells. Deletion of either HS2 or HS3 dramatically diminished the β-globin transcription and disrupted locus-wide histone H3K27ac and chromatin interaction between LCR HSs and gene. Surprisingly, ΔHS2 weakened interactions between CTCF sites forming the β-globin topologically associating domain (TAD), while ΔHS3 did not. CTCF occupancy and chromatin accessibility were reduced at the CTCF sites in the ΔHS2 locus. To further characterize the HS2, we deleted the maf-recognition elements for erythroid activator NF-E2 at HS2. This deletion decreased the β-globin transcription and enhancer-promoter interaction, but did not affect interactions between CTCF sites for the TAD. In light of these results, we propose that the HS2 has a role in forming a β-globin TAD by activating neighboring CTCF sites and this role is beyond typical enhancer activity. [ABSTRACT FROM AUTHOR]

Abstract Background The spatial organization of the mammalian genome relies upon the formation of chromatin domains of various scales. At the level of gene regulation in cis, collections of enhancer sequences define large regulatory landscapes that usually match with the presence of topologically associating domains (TADs). These domains often contain ranges of enhancers displaying similar or related tissue specificity, suggesting that in some cases, such domains may act as coherent regulatory units, with a global on or off state. By using the HoxD gene cluster, which specifies the topology of the developing limbs via highly orchestrated regulation of gene expression, as a paradigm, we investigated how the arrangement of regulatory domains determines their activity and function. Results Proximal and distal cells in the developing limb express different levels of Hoxd genes, regulated by flanking 3′ and 5′ TADs, respectively. We characterized the effect of large genomic rearrangements affecting these two TADs, including their fusion into a single chromatin domain. We show that, within a single hybrid TAD, the activation of both proximal and distal limb enhancers globally occurred as when both TADs are intact. However, the activity of the 3′ TAD in distal cells is generally increased in the fused TAD, when compared to wild type where it is silenced. Also, target gene activity in distal cells depends on whether or not these genes had previously responded to proximal enhancers, which determines the presence or absence of H3K27me3 marks. We also show that the polycomb repressive complex 2 is mainly recruited at the Hox gene cluster and can extend its coverage to far-cis regulatory sequences as long as confined to the neighboring TAD structure. Conclusions We conclude that antagonistic limb proximal and distal enhancers can exert their specific effects when positioned into the same TAD and in the absence of their genuine target genes. We also conclude that removing these target genes reduced the coverage of a regulatory landscape by chromatin marks associated with silencing, which correlates with its prolonged activity in time.

Introduction. Collaboration between professional and higher education institutions and industrial enterprises, located within the city, is of high priority in the territories of advanced development (TAD).Materials and Methods. The paper presents the analysis of Russian and foreign research works aimed at studying the important issues of collaboration between state, professional and higher education institutions and industrial enterprises in educating specialists for industrial enterprises. The main focus is made on enterprises which are the residents of the territories of advanced development and the socio-economic conditions of establishing collaboration. The authors applied scholarly literature study methods, as well as questionnaire, analysis, and generalization and systematization of obtained data approach. Results. The authors have identified and described the main stakeholders of the collaboration, and derived criteria to evaluate the outcomes of education institutions and industrial enterprises collaboration and the efficiency level in training qualified personnel for TAD.Discussion and Conclusions. Future investigation in regard of finding methods and techniques to assess education institutions and industrial enterprises collaboration efficiency is required. Authors also aim at finding efficient collaboration factors which are more relevant to the conditions of territories of advanced development and focus specifically on medium and small-sized enterprises and education institutions of those territories. All the research findings might be used as structural elements of an ontological model of a digital monitoring support system at planning, managing and controlling the process of training specialists for industrial enterprises of TAD.

Thoracic aortic dissection (TAD) is an aortic disease associated with dysregulated extracellular matrix composition and de‐differentiation of vascular smooth muscle cells (SMCs). Growth Differentiation Factor 11 (GDF11) is a member of transforming growth factor β (TGF‐β) superfamily associated with cardiovascular diseases. The present study attempted to investigate the expression of GDF11 in TAD and its effects on aortic SMC phenotype transition. GDF11 level was found lower in the ascending thoracic aortas of TAD patients than healthy aortas. The mouse model of TAD was established by β‐aminopropionitrile monofumarate (BAPN) combined with angiotensin II (Ang II). The expression of GDF11 was also decreased in thoracic aortic tissues accompanied with increased inflammation, arteriectasis and elastin degradation in TAD mice. Administration of GDF11 mitigated these aortic lesions and improved the survival rate of mice. Exogenous GDF11 and adeno‐associated virus type 2 (AAV‐2)‐mediated GDF11 overexpression increased the expression of contractile proteins including ACTA2, SM22α and myosin heavy chain 11 (MYH11) and decreased synthetic markers including osteopontin and fibronectin 1 (FN1), indicating that GDF11 might inhibit SMC phenotype transition and maintain its contractile state. Moreover, GDF11 inhibited the production of matrix metalloproteinase (MMP)‐2, 3, 9 in aortic SMCs. The canonical TGF‐β (Smad2/3) signalling was enhanced by GDF11, while its inhibition suppressed the inhibitory effects of GDF11 on SMC de‐differentiation and MMP production in vitro. Therefore, we demonstrate that GDF11 may contribute to TAD alleviation via inhibiting inflammation and MMP activity, and promoting the transition of aortic SMCs towards a contractile phenotype, which provides a therapeutic target for TAD. [ABSTRACT FROM AUTHOR]

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Micro-osteoperforations is one of the non-invasive surgical techniques used in attempt to accelerate OTM. Conflicting reports on its effectiveness has been reported in the literature. The objectives of this trial were to investigate the effect of micro-osteoperforations on the rate of space closure and on molar anchorage loss during mini-implant supported maxillary anterior en-masse retraction. A single center, parallel arm, randomized controlled trial was conducted. Sixty, male and female subjects (age range 16–25 years) having Class I bimaxillary protrusion or Class II div 1 malocclusion, who required fixed mechanotherapy with either upper 1st premolar or all four 1st premolar extractions were allocated into two groups using 1:1 allocation ratio. The allocation was done by block randomization method with a block size of 6. In the experimental group, 5 MOPs per side were performed only once just before the en-masse anterior retraction. Mini-screws were placed in order to obtain maximum anchorage. Impressions were taken every month till 4 months and rate of space closure was measured on 3D study models. Data of 27 subjects in control (attrition ​= ​3) and 28 subjects in experimental group (attrition ​= ​2) were analyzed at the end of this trial. There was a statistically significant increase in the rate of en-masse retraction for the 1st month(p ​= ​0.001,95%CI, 0.17, 0.37 ​mm) but there was no statistically significant difference for the subsequent 2nd (p ​= ​0.450,95%CI,0.13,0.43 ​mm), 3rd(p ​= ​0.204,95%CI,0.23,0.47 ​mm) and 4th month (p ​= ​0.680,95%CI,0.21,0.41 ​mm) between experimental and control groups. There was also no difference (p ​> ​0.05) in molar anchorage loss between both groups at all time intervals. Micro-osteoperforations (MOPs) did not accelerate the rate of anterior en-masse retraction over a period of 4 months; however, it temporarily increases the rate of retraction only for first month and no affect on molar anchorage. The trial was registered at www.ctri.nic.in with CTRI No- CTRI/2019/03/018140). [ABSTRACT FROM AUTHOR]

Myofibres (primary and secondary myofibre) are the basic structure of muscle and the determinant of muscle mass. To explore the skeletal muscle developmental processes from primary myofibres to secondary myofibres in pigs, we conducted an integrative three-dimensional structure of genome and transcriptomic characterization of longissimus dorsi muscle of pig from primary myofibre formation stage [embryonic Day 35 (E35)] to secondary myofibre formation stage (E80). In the hierarchical genomic structure, we found that 11.43% of genome switched compartment A/B status, 14.53% of topologically associating domains are changed intradomain interactions (D -scores) and 2,730 genes with differential promoter–enhancer interactions and (or) enhancer activity from E35 to E80. The alterations of genome architecture were found to correlate with expression of genes that play significant roles in neuromuscular junction, embryonic morphogenesis, skeletal muscle development or metabolism, typically, NEFL , MuSK , SLN , Mef2D and GCK. Significantly, Sox6 and MATN2 play important roles in the process of primary to secondary myofibres formation and increase the regulatory potential score and genes expression in it. In brief, we reveal the genomic reorganization from E35 to E80 and construct genome-wide high-resolution interaction maps that provide a resource for studying long-range control of gene expression from E35 to E80. [ABSTRACT FROM AUTHOR]

Background: The three-dimensional spatial organization of the genome plays important roles in chromatin accessibility and gene expression in multiple biological processes and has been reported to be altered in response to environmental stress. However, the functional changes in spatial genome organization during environmental changes in crop plants are poorly understood. Results: Here we perform Hi-C, ATAC-seq, and RNA-seq in two agronomically important rice cultivars, Nipponbare (Nip; Japonica) and 93-11 (Indica), to report a comprehensive profile of nuclear dynamics during heat stress (HS). We show that heat stress affects different levels of chromosome organization, including A/B compartment transition, increase in the size of topologically associated domains, and loss of short-range interactions. The chromatin architectural changes were associated with chromatin accessibility and gene expression changes. Comparative analysis revealed that 93-11 exhibited more dynamic gene expression and chromatin accessibility changes, including HS-related genes, consistent with observed higher HS tolerance in this cultivar. Conclusions: Our data uncovered higher-order chromatin architecture as a new layer in understanding transcriptional regulation in response to heat stress in rice. [ABSTRACT FROM AUTHOR]

Objectives: Greater advancement of the maxilla can be achieved with skeletal-anchored facemasks (SAFM) using miniplates than with conventional tooth-borne facemasks (TBFM). The purpose of this study was to compare the effects of TBFM and SAFM on midfacial soft tissue and nasal bone up to two years after treatment.Settings and Sample Population: Sixty-seven growing patients with Class III malocclusions were treated with facemasks. They were divided into a SAFM group with 31 subjects (average age 11.1 years) and a TBFM group with 36 subjects (average age 11.0 years).Materials and Methods: Cephalometric analysis was conducted using linear and angular midfacial measurements. Lateral cephalograms were taken initially (T0), after treatment (T1) and at two years post-treatment (T2). Significance was assessed between the two groups.Results: Comparing changes in the midfacial area between the SAFM and TBFM groups during the traction period (T0-T1), angular measurements such as SNOr (1.34°), nasolabial angle (4.20°), nasal angles 1 and 2 (1.23°, 2.14°) and linear measurements such as Prn, Sn, A' distance (approximately 2 mm) increased significantly more in the SAFM group. Over the entire treatment period (T0-T2), the changes in SNOr (1.33°), nasolabial angle (6.54°), nasal angles 1 and 2 (1.45°, 2.99°) and Prn, Sn, A' distance (approximately 2 mm) remained significant (P < .05).Conclusions: In the treatment of growing patients with Class III malocclusions with maxillary deficiency, it was possible to achieve significantly greater advancement in the midfacial area with SAFM treatment than with TBFM treatment. This significant difference was well maintained at two years post-treatment. [ABSTRACT FROM AUTHOR]

Objectives: Greater advancement of the maxilla can be achieved with skeletal‐anchored facemasks (SAFM) using miniplates than with conventional tooth‐borne facemasks (TBFM). The purpose of this study was to compare the effects of TBFM and SAFM on midfacial soft tissue and nasal bone up to two years after treatment. Settings and Sample Population: Sixty‐seven growing patients with Class III malocclusions were treated with facemasks. They were divided into a SAFM group with 31 subjects (average age 11.1 years) and a TBFM group with 36 subjects (average age 11.0 years). Materials and Methods: Cephalometric analysis was conducted using linear and angular midfacial measurements. Lateral cephalograms were taken initially (T0), after treatment (T1) and at two years post‐treatment (T2). Significance was assessed between the two groups. Results: Comparing changes in the midfacial area between the SAFM and TBFM groups during the traction period (T0‐T1), angular measurements such as SNOr (1.34°), nasolabial angle (4.20°), nasal angles 1 and 2 (1.23°, 2.14°) and linear measurements such as Prn, Sn, A' distance (approximately 2 mm) increased significantly more in the SAFM group. Over the entire treatment period (T0‐T2), the changes in SNOr (1.33°), nasolabial angle (6.54°), nasal angles 1 and 2 (1.45°, 2.99°) and Prn, Sn, A' distance (approximately 2 mm) remained significant (P <.05). Conclusions: In the treatment of growing patients with Class III malocclusions with maxillary deficiency, it was possible to achieve significantly greater advancement in the midfacial area with SAFM treatment than with TBFM treatment. This significant difference was well maintained at two years post‐treatment. [ABSTRACT FROM AUTHOR]

Background: Three-dimensional chromatin loop structures connect regulatory elements to their target genes in regions known as anchors. In complex plant genomes, such as maize, it has been proposed that loops span heterochromatic regions marked by higher repeat content, but little is known on their spatial organization and genome-wide occurrence in relation to transcriptional activity. Results: Here, ultra-deep Hi-C sequencing of maize B73 leaf tissue was combined with gene expression and open chromatin sequencing for chromatin loop discovery and correlation with hierarchical topologically-associating domains (TADs) and transcriptional activity. A majority of all anchors are shared between multiple loops from previous public maize high-resolution interactome datasets, suggesting a highly dynamic environment, with a conserved set of anchors involved in multiple interaction networks. Chromatin loop interiors are marked by higher repeat contents than the anchors flanking them. A small fraction of high-resolution interaction anchors, fully embedded in larger chromatin loops, co-locate with active genes and putative protein-binding sites. Combinatorial analyses indicate that all anchors studied here co-locate with at least 81.5% of expressed genes and 74% of open chromatin regions. Approximately 38% of all Hi-C chromatin loops are fully embedded within hierarchical TAD-like domains, while the remaining ones share anchors with domain boundaries or with distinct domains. Those various loop types exhibit specific patterns of overlap for open chromatin regions and expressed genes, but no apparent pattern of gene expression. In addition, up to 63% of all unique variants derived from a prior public maize eQTL dataset overlap with Hi-C loop anchors. Anchor annotation suggests that < 7% of all loops detected here are potentially devoid of any genes or regulatory elements. The overall organization of chromatin loop anchors in the maize genome suggest a loop modeling system hypothesized to resemble phase separation of repeat-rich regions. Conclusions: Sets of conserved chromatin loop anchors mapping to hierarchical domains contains core structural components of the gene expression machinery in maize. The data presented here will be a useful reference to further investigate their function in regard to the formation of transcriptional complexes and the regulation of transcriptional activity in the maize genome. [ABSTRACT FROM AUTHOR]