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Energy use, together with consumption of raw materials, machine clothing, and wet end chemicals, are some of the most critical aspects in successful tissue making today. This work was aimed at developing a laboratory-scale method of estimating dewatering mechanisms, vacuum efficiency, and energy use of Through Air Drying (TAD) of tissue. When compared to pilot data, the results of the new laboratory method for investigating dewatering during TAD were in the same magnitude, around 24 to 26% dryness after vacuum dewatering, and 27 to 29% dryness after TAD molding. Sheet properties, such as caliper and surface profile, were evaluated and compared to commercial tissue sheets. The results indicate that it will be possible to precisely measure accurate dryness development and penetrated air volume for tissue sheet forming and TAD molding at a laboratory scale. This can contribute to the efforts of implementing a circular forest-based bioeconomy by increasing the fundamental understanding of dewatering of tissue paper materials, which is facilitated by improvements in energy use. The new method developed in this work will make it easier to assess ideas that are difficult to bring to pilot scale or full scale before learning more of the dewatering capabilities. The authors are convinced that improved knowledge of tissue dewatering mechanisms, forming, and material transport during and after TAD dewatering can increase the efficiency of the industrial manufacturing processes.

The study of the secondary-tertiary transition requires taking into account institutional evolution but also the point of view of the actors. For this reason we have chosen to network the activity theory adapted to the didactics of mathematics with the anthropological theory of the didactic. In this article we present this networking and illustrate its use through the example of conditional probabilities. We propose to operationalize the complementarity of these two theories by making use of the concept of type of tasks’ variations that we define and illustrate through the example presented. The new theoretical framework constructed allows us to describe praxeologies taught while taking into account the cognitive and mediative dimensions of the subject’s activity. L’étude de la transition secondaire-supérieur nécessite de prendre en compte les évolutions institutionnelles, mais également le point de vue des acteurs. C’est pourquoi nous avons choisi d’articuler la théorie de l’activité adaptée à la didactique des mathématiques avec la théorie anthropologique du didactique. Dans cet article, nous présentons cette articulation et nous illustrons son emploi à travers l’exemple des probabilités conditionnelles. Nous proposons d’opérationnaliser la complémentarité de ces deux théories au moyen du concept de variation de type de tâches que nous définissons et illustrons à travers l’exemple présenté. Le nouveau cadre théorique ainsi construit nous permet notamment de décrire les praxéologies enseignées tout en prenant en compte les dimensions cognitives et médiatives de l’activité du sujet.

Resumo Neste trabalho apresentamos um estudo das condições e restrições que incidem sobre um percurso de estudo e pesquisa (PEP) ao utilizá-lo para o ensino de cônicas (parábola, elipse e hipérbole) a um grupo de estudantes do terceiro ano do Ensino Médio de Itabaiana/Sergipe/Brasil. A pesquisa seguiu a metodologia da teoria antropológica do didático que é baseada em princípios da Engenharia Didática e que possui quatro fases. Na primeira foram desenvolvidos os estudos epistemológico e econômico, na segunda realizamos a análise a priori e o planejamento do PEP, que foi experimentado na terceira fase e, por fim, na quarta, realizamos a análise a posteriori do experimento vivido. O planejamento, a construção e a gestão do PEP em sala de aula tiveram como base um modelo epistemológico de referência (MER) a respeito de cônicas, que mostra o estudo desse objeto em três modelos de geometria: sintética, analítica e linear. Os resultados apontam para um conjunto de condições e restrições, originadas do modelo de ensino atual, em que a instituição cobra do professor o cumprimento do conteúdo em determinado prazo; em que os alunos, não habituados com um dispositivo didático baseado em uma investigação, apresentam dificuldades no processo de elaboração de questões, no uso de fontes confiáveis de pesquisa na Internet, na falta de critérios para validar os conteúdos encontrados e no trabalho com elementos da geometria sintética. Abstract In this work, we present a study of the conditions and constraints that affect a study and research path (SRP) when using it to teach conics (parabola, ellipse, and hyperbola) with a group of third-year High School students of Itabaiana/Sergipe/Brazil. The research followed the anthropological didactic theory methodology, which is based on the principles of didactical engineering and has four steps. In the first one, we developed epistemological and economic studies, in the second one we carried out the a priori analysis and the design of the SRP, which was implemented in the third step and, finally, the last one corresponds to the a posteriori analysis of the implementation. The design and management of the SRP were based on a reference epistemological model (REM), that shows conics present in three geometry models: synthetic, analytical, and linear. The results point to a set of conditions and constraints originated from the current teaching paradigm, in which the institution requires the teacher to comply with the content within a certain period; in which students, who are not used to classes based on inquiries, present difficulties in the process of elaborating questions, the use of reliable research sources, finding criteria to validate contents found on the internet, and when they work with synthetic geometry.

Background Stevens-Johnson syndrome is a rare medical condition with severe mucocutaneous lesions due to adverse drug reactions characterized by exudative multiform erythema, stomatitis, and conjunctivitis. Long-term oral consequences of such cases include xerostomia, caries, impactions, and multiple dental developmental aberrations as short root anomalies. Aim and objective To highlight the role of pedodontist in early diagnosis and treatment planning of dental abnormalities due to Stevens-Johnson syndrome (SJS) using a cone-beam computed tomography (CBCT). Case description A 16-year-old male reported a chief complaint of decayed posterior teeth. Past medical history revealed adverse reactions to an unknown drug at the age of 4 to 5 years. In addition to carious teeth, clinical examination revealed that all canines were missing along with mandibular incisors. On CBCT examination, abnormal short, plump roots with normal crown were seen in all permanent first molars and incisors along with impacted canines and mandibular incisors. This condition was diagnosed as a "Short root anomaly" (SRA) due to SJS. He was found positive to allergy tests for NSAIDs such as ibuprofen and paracetamol. Conclusion NSAIDs can cause a severe adverse reaction resulting in SJS. If this hypersensitivity reaction occurs early during the development of a permanent tooth it may cause dental anomalies such as short roots, root dysmorphia, agenesis, and multiple impacted teeth. Clinical significance This report highlights a unique case of multiple dental aberrations due to SJS and the role of a pedodontist in the early diagnosis and treatment planning of such cases with the help of CBCT. Short root anomalies can be misdiagnosed as root resorption or immature apex. Medical history, clinical and CBCT findings are essential for diagnosis and treatment in SJS patients. Careful orthodontic treatment planning is required in cases of short root anomalies. How to cite this article Katyal S, Yadav V. Diagnostic and Treatment Approach in the Management of Dental Anomalies Associated with Stevens-Johnson Syndrome: A Case Report. Int J Clin Pediatr Dent 2021;14(4):569-574.

In eukaryotes, the genome is hierarchically packed inside the nucleus, which facilitates physical contact between cis-regulatory elements (CREs), such as enhancers and promoters. Accumulating evidence highlights the critical role of higherorder chromatin structure in precise regulation of spatiotemporal gene expression under diverse biological contexts including lineage commitment and cell activation by external stimulus. Genomics and imaging-based technologies, such as Hi-C and DNA fluorescence in situ hybridization (FISH), have revealed the key principles of genome folding, while newly developed tools focus on improvement in resolution, throughput and modality at single-cell and population levels, and challenge the knowledge obtained through conventional approaches. In this review, we discuss recent advances in our understanding of principles of higher-order chromosome conformation and technologies to investigate 4D chromatin interactions. [BMB Reports 2021; 54(5): 233-245].

Graphical abstract, 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.

The mechanisms underlying long-range interactions between chromatin regions and the principles of chromosomal architecture formation are currently under extensive scrutiny. A special class of regulatory elements known as insulators is believed to be involved in the regulation of specific long-range interactions between enhancers and promoters. This review focuses on the insulators of Drosophila and mammals, and it also briefly characterizes the proteins responsible for their functional activity. It was initially believed that the main properties of insulators are blocking of enhancers and the formation of independent transcription domains. We present experimental data proving that the chromatin loops formed by insulators play only an auxiliary role in enhancer blocking. The review also discusses the mechanisms involved in the formation of topologically associating domains and their role in the formation of the chromosomal architecture and regulation of gene transcription.

Eukaryotic genomes are structurally organized via the formation of multiple loops that create gene expression regulatory units called topologically associating domains (TADs). Here we revealed the KSHV TAD structure at 500 base pair resolution and constructed a 3D KSHV genomic structural model with 2kb binning. The latent KSHV genome formed very similar genomic architectures in three different naturally infected PEL cell lines and in an experimentally infected epithelial cell line. The majority of the TAD boundaries were occupied by CTCF and SMC1, and the KSHV transactivator was recruited to these sites during reactivation. Triggering KSHV gene expression decreased pre-wired genomic loops within the regulatory unit, while contacts extending outside of regulatory borders increased, leading to formation of a larger regulatory unit with a shift from repressive to active compartments (B to A). The 3D genomic structural model proposes that the immediate-early promoter region is localized on the periphery of the 3D viral genome during latency, while highly inducible non-coding RNA regions moved toward the inner space of the structure, resembling the configuration of a “bird cage” during reactivation. The compartment-like properties of viral episomal chromatin structure and its reorganization during the transition from latency may help coordinate viral gene transcription.ImportanceThe 3D architecture of chromatin allows for efficient arrangement, expression, and replication of genetic material. The genomes of all organisms studied to date have been found to be organized through some form of tiered domain structures. However, the architectural framework of the genomes of large double-stranded DNA viruses such as the herpesvirus family has not been reported. Prior studies with Kaposi’s sarcoma-associated herpesvirus (KSHV) have indicated that the viral chromatin shares many biological properties exhibited by the host cell genome, essentially behaving as a mini human chromosome. Thus, we hypothesized that the KSHV genome may be organized in a similar manner. In this report, we describe the domain structure of the latent and lytic KSHV genome at 500 base pair resolution and present a 3D genomic structural model for KSHV under each condition. These results add new insights into the complex regulation of the viral lifecycle.

Enhancers and promoters are DNA sequences whose physical proximity, through chromatin looping, is a necessary condition to initiate gene transcription. Functional chromatin interactions are limited by topologically associating domains (TADs), structural regulatory units of the genome that constrain enhancer-promoter crosstalk. Recent studies have elucidated that an important role of the CCCTC-binding factor (CTCF) regulates in theT processes of TAD and loop formation. However, it remains unclear whether CTCF is indispensable to mediate enhancers-promoter interactions and to achieve precise spatio-temporal patterns of gene expression during development. To investigate this, we systematically deleted CTCF-binding motifs at the Epha4 locus in mice using CRISPR-Cas9 and evaluated the effects on chromatin organization and gene expressionfunctional consequences in vivo. We focused on two CTCF sites associated to an enhancer-promoter interaction that occurs during mouse limb development. Analysis of genome architecture showed that CTCF binding site deletions induce a complete depletion of enhancer-promoter interactions. Analysis of Epha4 expression levels revealed that while the enhancer-promoter loop is disrupted, up to 50% of physiological expression levels are be retained. Our results suggest that the baseline proximity generated by topologically associated domains (TADs can be sufficient to fail-safe expressional output during developmentis sufficient to yield a certain amount of expressional output. Previous research on TADs has stressed their insulating properties - highlighting their function of restricting enhancer-promoter contacts over TAD boundaries. Our results stresshighlight an additional function of TADs in supporting enhancer-promoter communication and in sustaining developmental gene expression., Enhancer und Promotoren sind DNA-Sequenzen, deren physische Nähe durch Chromatin-Schleifenbildung eine notwendige Voraussetzung für die Einleitung von Gentranskription ist. Solche Enhancer-Promoter-Interaktionen werden durch topologisch assoziierende Domänen (TADs) eingeschränkt. Neuere Studien haben gezeigt, dass der CCCTC-Bindungsfaktor (CTCF) die TAD und Chromatin-Schleifenbildung reguliert. Es bleibt jedoch unklar, ob CTCF unverzichtbar ist, um Enhancer-Promoter-Interaktionen zu vermitteln und präzise räumlich-zeitliche Muster von Genexpression während der Entwicklung zu erzielen. Um dies zu untersuchen, haben wir mit CRISPR-Cas9 systematisch CTCF-Bindungsmotive am E-pha4-Locus bei Mäusen deletiert und die Auswirkungen auf Genexpression und Chromatin-Architektur in vivo ausgewertet. Wir konzentrierten uns auf zwei Bindungsmotive, die mit einer Enhancer-Promoter-Interaktion verbunden sind, welche während der Entwicklung der Extremitäten der Maus auftritt. Die Analyse der Genomarchitektur zeigte, dass die Deletionen der CTCF-Bindungsstelle eine vollständige Erschöpfung der Enhancer-Promoter-Interaktionen induzieren. Die Analyse der Epha4- Expressionsniveaus zeigte, dass während die Enhancer-Promoter-Schleife unterbrochen ist, bis zu 50% des physiologischen Expressionsniveaus erhalten bleiben. Unsere Ergebnisse deuten darauf hin, dass die durch topologisch assoziierte Domänen (TADs) erzeugte Basisfrequenz an Enhancer-Promoter-Kontakten ausreicht, um eine bestimmte Menge an expressivem Output zu erzielen. Frühere Forschungen über TADs haben hauptsächlich ihre isolierenden Eigenschaften betont - und ihre Funktion der Einschränkung von Enhancer-Promoter-Kontakten über TAD-Grenzen hinweg hervorgehoben. Unsere Ergebnisse unterstreichen eine zusätzliche Funktion von TADs bei der Unterstützung der Enhancer-Promotor-Kommunikation und bei der Aufrechterhaltung von Genexpression in der Entwicklung.

In mammals, most of the boundaries of topologically associating domains and all well-studied insulators are rich in binding sites for the CTCF protein. According to existing experimental data, CTCF is a key factor in the organization of the architecture of mammalian chromosomes. A characteristic feature of the CTCF is that the central part of the protein contains a cluster consisting of eleven domains of C2H2-type zinc fingers, five of which specifically bind to a long DNA sequence conserved in most animals. The class of transcription factors that carry a cluster of C2H2-type zinc fingers consisting of five or more domains (C2H2 proteins) is widely represented in all groups of animals. The functions of most C2H2 proteins still remain unknown. This review presents data on the structure and possible functions of these proteins, using the example of the vertebrate CTCF protein and several well- characterized C2H2 proteins in Drosophila and mammals.

Graphical abstract, Highlights • N-terminal domain of SpTad2/3 is a putative kinase but not functional. • N-SpTad2 does not bind tRNA but its deletion renders the deaminase inactive. • Structure of N-SpTad2 was solved, revealing it may bind phosphates. • Incapable of binding to DNA, N-SpTad2 may enhance the stability of the holoenzyme., 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.

This study was designed to demonstrate the effects of surgical skills of final-year veterinary medicine students relating to total surgery time and skin incision length on postoperative stress, oxidative stress and pain in bitches undergoing ovariohysterectomy under identical anaesthesia and surgical procedures. The control group (n=12) consisted of bitches that were operated on by an experienced surgeon, while the ovariohysterectomies in the experiment group (n=12) were performed by final-year veterinary medicine students. Blood samples were taken 24 hours before the surgery, during premedication, at the end of surgery and 30 minutes, 1, 2, 4 and 6 hours after surgery for the analysis of cortisol, total oxidant status (TOS), total antioxidant status (TAS) and for the calculation of the oxidative stress index (OSI). Modified Melbourne Pain Scale was used for pain assessment. It was observed that the total surgery time and length of skin incision in the experiment group were significantly higher (p, SSunulan çalışmada, veteriner hekimliği eğitiminin son sınıfında olan öğrencilerin, toplam operasyon süresi ve deri ensizyonu uzunluğu ile ilişkili olan cerrahi becerilerinin operasyon sonrası stres, oksidatif stres ve ağrı üzerine etkilerinin aynı anestezi ve cerrahi prosedürler altında ortaya konulması amaçlandı. Tecrübeli bir hekimin opere ettiği köpekler kontrol grubunu (n=12) oluştururken, veteriner fakültesi son sınıfta eğitim gören öğrenciler tarafından opere edilen köpekler (n=12) deneme grubunu oluşturdu. Operasyondan 24 saat önce, premedikasyon sırasında, operasyon sonunda ve operasyondan 30 dakika, 1, 2, 4 ve 6 saat sonra kan örnekleri toplanarak kortizol, toplam oksidant durum (TOD), toplam antioksidant durum (TAD) ölçüldü ve oksidatif stress indeksi (OSI) hesaplandı. Modifiye edilmiş Melbourne Ağrı Skalası ağrı değerlendirilmesi için kullanıldı. Deneme grubundaki köpeklerde, toplam operasyon süresi ve deri ensizyon uzunluğunun kontrol grubundaki köpeklerden istatistiksel olarak (p

Precise spatiotemporal gene expression during embryonic developmental is controlled by cis- regulatory elements (CREs) such as enhancers and promoters. Their physical chromatin proximity is correlated with active transcription and thought to be restricted to topologically associated domains (TADs) that help establish interactions between CREs and limit inappropriate contacts. Accordingly, TADs frequently overlap with gene regulatory landscapes, in which are contained diverse enhancers that transmit their activity across the domain towards their target promoter. Large structural variants reorganizing TADs were shown to cause gene misexpression and disease thereby linking gene regulation to chromatin structure. Recently, several studies revealed controversial results questioning the importance of TADs for transcriptional control. Acute depletion of CTCF and other architectural proteins in vitro led to loss of TAD structures with surprisingly modest effects on gene expression. However, the cytotoxicity of such depletion assays hindered analysis of more complex gene regulatory scenarios and their effect during development. This study specifically addresses the connection between TADs and developmental gene regulation through two projects using the murine limb as a model system. First, we took advantage of the Sox9/Kcnj2-locus that is subdivided into two adjacent TADs with distinct expression patterns of Sox9 and Kcnj2. The systematic deletion of individual CTCF binding sites at the TAD boundary and within the TAD resulted in gradual fusion of the neighboring domains without major effects on gene expression. TAD rearrangement by TAD-spanning inversions and repositioning of the boundary, however, redirected the regulatory activity and resulted in pathogenic gene misexpression. Thus, TAD structures may not be essential for developmental gene regulation, yet CTCF-dependent rearrangement of TADs can lead to the redirection of enhancer–promoter contacts and gene misexpression. In the second project, we studied how enhancer position relative to its TAD influences the function of an individual enhancer at the Shh-locus. Therefore, we repositioned the Shh-limb enhancer ZRS to five alternative locations inside and outside of its TAD. As expected, the enhancer lost all function in the positions outside of the Shh-TAD. Interestingly, the new positions inside the TAD also displayed decreased enhancer activity, albeit to varying degrees. Further analysis suggests that CTCF likely functions in some positions as a facilitator of enhancer-promoter contacts, while insulating short-range contacts in others. Ultimately, the ZRS is only able to ectopically activate some genes if repositioned to novel TADs, displaying strong enhancer-promoter selectivity. In summary, the results demonstrate that TADs provide robustness and precision to gene regulation, guiding enhancer-promoter interaction without being essential. The findings in this work build a basis for future studies aiming to understand enhancer-promoter interaction and can help in contextualizing potential disease-causing mutations disrupting TADs.

The tridimensional (3D) organization of the genome is just beginning to be understood and, despite the tremendous progress witnessed in the recent years, many essential questions remain unanswered. Major methodological and conceptual challenges need to be overcome to reach a comprehensive view of the physiological impact of 3D genome architecture in health and disease. CSIC is in a privileged position to undertake these challenges

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.

Animal genomes are organized into topologically associated domains (TADs), which exhibit more intra-domain than inter-domain contact. However, the absolute difference in contact is usually no more than twofold, even though disruptions to TAD boundaries can change gene expression by 8-10 fold. Existing models fail to explain this superlinear transcriptional response to changes in genomic contact. Here, we propose a futile cycle model where an enzyme stimulated by association with its products can exhibit bistability and hysteresis, allowing a small increase in enhancer-promoter contact to produce a large change in expressionwithoutobvious correlation between E-P contact and promoter activity. Through mathematical analysis and stochastic simulation, we show that this system can create an illusion of enhancer-promoter specificity and explain the importance of weak TAD boundaries. It also offers a mechanism to reconcile recent global cohesin loop disruption and TAD boundary deletion experiments. We discuss the model in the context of these recent controversial experiments. Together, these analyses advance our interpretation and understanding of cis-regulatory contacts in controlling gene expression, and suggest new experimental directions.

La laïcité représente le cadre général dans lequel s’exprime l’enseignement scolaire, mais dans le cadre de l’histoire secondaire, elle représente aussi un objet d’enseignement. Elle renvoie à des évènements historiques, la laïcisation de la société sous la IIIe République, que nous retrouvons en quatrième et en première, mais pas seulement. Elle renvoie aussi, dans l’éphémère programme de terminale de 2012 à la situation des États-Unis d’Amérique qui en donne une construction exotique. Pour autant, le fait se construit toujours dans le cadre d’un récit plus vaste. Cette laïcité reçoit des incarnations et des contours différents en fonctions des niveaux dans lesquels les manuels la racontent. À travers l’analyse des manuels et dans le cadre de la TAD, nous tenterons de montrer comment la laïcité reste tributaire de contraintes qui l’encadrent. Secularism is the general frame of public education, but it is also taught as a subject in secondary education. It conjures up historical events, as the secularisation of the society during the 3rd Republic, seen in the classes of quatrième and première, but not only. It also refers to the temporary 2012 Terminale curriculum and the situation of the United States of America where it represents more exotic an object. But the fact always constructs itself in a wider narration frame. This secularism get different embodiments and shapes according to the class the textbooks are taught it in. Through those textbooks analysis and in the frame of the ATD, we will try to demonstrate how secularism stays framed by a number of constraints.

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.

International audience; Our article deals with teachers in Master Teacher Training Schools (MTTS), considered essential in the French education system for their teaching and training mission and subject to an institutional context that gives a significant weight to their commitment to pedagogical innovation. We propose to use a case study to examine the praxeological development of a teacher trainer who has been little studied in the context of a research training program based on the framework of the anthropological theory of didactics (Chevallard, 1998).; Notre article concerne des Professeurs des Écoles Maîtres Formateurs (PEMF), considérés comme essentiels dans le système éducatif français pour leur mission d’enseignement et leur mission de formation et soumis à un contexte institutionnel qui donne un poids important à leur engagement dans des démarches d’innovation pédagogique. Nous proposons d’interroger à partir d’une étude de cas le développement praxéologique d’un formateur d’enseignants qui reste peu étudié dans un Dispositif de Recherche Faisant Formation à partir du cadre de la théorie anthropologique du didactique (Chevallard, 1998).

Collinear regulation of Hox genes in space and time has been an outstanding question ever since the initial work of Ed Lewis in 1978. Here we discuss recent advances in our understanding of this phenomenon in relation to novel concepts associated with large-scale regulation and chromatin structure during the development of both axial and limb patterns. We further discuss how this sequential transcriptional activation marks embryonic stem cell-like axial progenitors in mammals and, consequently, how a temporal genetic system is further translated into spatial coordinates via the fate of these progenitors. In this context, we argue the benefit and necessity of implementing this unique mechanism as well as the difficulty in evolving an alternative strategy to deliver this critical positional information.

Summary: Intergenic long noncoding RNAs (lincRNAs) are the largest class of transcripts in the human genome. Although many have recently been linked to complex human traits, the underlying mechanisms for most of these transcripts remain undetermined. We investigated the regulatory roles of a high-confidence and reproducible set of 69 trait-relevant lincRNAs (TR-lincRNAs) in human lymphoblastoid cells whose biological relevance is supported by their evolutionary conservation during recent human history and genetic interactions with other trait-associated loci. Their enrichment in enhancer-like chromatin signatures, interactions with nearby trait-relevant protein-coding loci, and preferential location at topologically associated domain (TAD) boundaries provide evidence that TR-lincRNAs likely regulate proximal trait-relevant gene expression in cis by modulating local chromosomal architecture. This is consistent with the positive and significant correlation found between TR-lincRNA abundance and intra-TAD DNA-DNA contacts. Our results provide insights into the molecular mode of action by which TR-lincRNAs contribute to complex human traits. : Tan et al. identify and characterize 69 human complex trait/disease-associated lincRNAs in LCLs. They show that these loci are often associated with cis-regulation of gene expression and tend to be localized at TAD boundaries, suggesting that these lincRNAs may influence chromosomal architecture. Keywords: intergenic long noncoding RNA, lincRNA, GWAS, expression quantitative trait loci, eQTL, complex trait and disease, enhancer, cis-regulation, topologically associated domains, TAD

The fusion of two transcriptionally silent gametes, egg and sperm, generates a totipotent zygote that activates zygotic transcription to support further development. Although the molecular details of zygotic genome activation (ZGA) are not well understood in most species, an emerging concept is that one or more pioneer transcription factors trigger zygotic transcription. Concomitantly, extensive changes in 3D chromatin organization occur during development. In this review, we discuss recent advances in understanding when and how genome architecture emerges in early metazoan embryos, how the zygotic genome is activated, and how these events might be coordinated. We also highlight some of the unknowns that may be critical to address in the future.

Mammalian genomes are folded into topologically associating domains (TADs), consisting of chromatin loops anchored by CTCF and cohesin. Some loops are cell-type specific. Here we asked whether CTCF loops are established by a universal or locus-specific mechanism. Investigating the molecular determinants of CTCF clustering, we found that CTCF self-association invitro is RNase sensitive and that an internal RNA-binding region (RBRi) mediates CTCF clustering and RNA interaction invivo. Strikingly, deleting the RBRi impairs about half of all chromatin loops in mESCs and causes deregulation of gene expression. Disrupted loop formation correlates with diminished clustering and chromatin binding of RBRi mutant CTCF, which in turn results in a failure to halt cohesin-mediated extrusion. Thus, CTCF loops fall into at least two classes: RBRi-independent and RBRi-dependent loops. We speculate that evidence for RBRi-dependent loops may provide a molecular mechanism for establishing cell-specific CTCF loops, potentially regulated by RNA(s) or other RBRi-interacting partners.

Hip fractures are associated with a 20% one-year mortality and a 50% loss of function. Over 700,000 deaths are estimated to occur annually worldwide following hip fractures. Concern exist regarding which is the best implant for extracapsular fractures fixation. For a correct positioning of the cephalic screw, a new plate (O'Nil Anteversa® mini-plate, Intrauma, Torino, Italy) with a fixed 8°of anteversion in the axial plane was developed. A total of 22 patients with an intertrochanteric fracture underwent surgery with Anteversa® mini-plate between October 2016 and April 2017. Data collected included patients' age at surgery, gender, fracture type, operative side, surgeon, type of implant, TAD, CalTAD and TADCalTAD. All patients underwent clinical and radiographic evaluations according to the AO Surgery Reference classification. The mean TAD, CalTAD and TADcalTAD for the entire population of study were, respectively, 20.18±7.5 mm, 20.45±7.25 mm, and 40.62±14.44 mm. The mean TAD, CalTAD and TADcalTAD of those patients who experienced mobilisation of the cephalic screw were, respectively, 20.26±5.87 mm, 19.53±5.47 mm, and 39.8±11.16 mm. Three patients experienced mobilisation of the cephalic screw, and none of these had a TAD greater than 25 mm, a CalTAD greater of 25mm or a TADcalTAD greater than 50 mm. This type of device meets the essential requirements for a correct treatment of intertrochanteric fractures in elderly patients. However, the excessive need of attention in each step, and the consequent increased time of surgery, could be seen as a limitation for its use.

© 2020 Elsevier Inc. Whereas folding of genomes at the large scale of epigenomic compartments and topologically associating domains (TADs) is now relatively well understood, how chromatin is folded at finer scales remains largely unexplored in mammals. Here, we overcome some limitations of conventional 3C-based methods by using high-resolution Micro-C to probe links between 3D genome organization and transcriptional regulation in mouse stem cells. Combinatorial binding of transcription factors, cofactors, and chromatin modifiers spatially segregates TAD regions into various finer-scale structures with distinct regulatory features including stripes, dots, and domains linking promoters-to-promoters (P-P) or enhancers-to-promoters (E-P) and bundle contacts between Polycomb regions. E-P stripes extending from the edge of domains predominantly link co-expressed loci, often in the absence of CTCF and cohesin occupancy. Acute inhibition of transcription disrupts these gene-related folding features without altering higher-order chromatin structures. Our study uncovers previously obscured finer-scale genome organization, establishing functional links between chromatin folding and gene regulation.

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.

The organisation of mammalian genomes into loops and topologically associating domains (TADs) contributes to chromatin structure, gene expression and recombination. Loops and TADs are formed by cohesin and positioned by CTCF. In proliferating cells, cohesin also mediates sister chromatid cohesion, which is essential for chromosome segregation. Current models of chromatin folding and cohesion are based on assumptions of how many cohesin and CTCF molecules organise the genome. Here we have measured absolute copy numbers and dynamics of cohesin, CTCF, NIPBL, WAPL and sororin by mass spectrometry, fluorescence-correlation spectroscopy and fluorescence recovery after photobleaching in HeLa cells. In G1-phase there are ~245,000 cohesin complexes, of which ~139,000 are on chromatin. Comparison with chromatin immunoprecipitation-sequencing data implies that some genomic cohesin and CTCF enrichment sites are unoccupied in single cells at any one time. We discuss the implications of these findings for how cohesin can contribute to genome organisation and cohesion.

Achieving a quantitative and predictive understanding of 3D genome architecture remains a major challenge, as it requires quantitative measurements of the key proteins involved. Here, we report the quantification of CTCF and cohesin, two causal regulators of topologically associating domains (TADs) in mammalian cells. Extending our previous imaging studies (Hansen et al., 2017), we estimate bounds on the density of putatively DNA loop-extruding cohesin complexes and CTCF binding site occupancy. Furthermore, co-immunoprecipitation studies of an endogenously tagged subunit (Rad21) suggest the presence of cohesin dimers and/or oligomers. Finally, based on our cell lines with accurately measured protein abundances, we report a method to conveniently determine the number of molecules of any Halo-tagged protein in the cell. We anticipate that our results and the established tool for measuring cellular protein abundances will advance a more quantitative understanding of 3D genome organization, and facilitate protein quantification, key to comprehend diverse biological processes.

Hoy en día la docencia está atravesando cambios de gran magnitud debido a la modernización de las infraestructuras y de las herramientas docentes, que intentan aportar una educación más eficiente para los alumnos y de más calidad. Principalmente, se espera que el rendimiento académico del estudiante aumente y que tengan una interacción más elevada con las herramientas que ofrece el docente. Este es el caso de la utilización de guías docentes que aportan al docente una visualización de como fomentar un aprendizaje con estrategias determinadas que ayuden a que los alumnos se impliquen y avancen en la materia de forma inclusiva. En la actualidad cada vez son más los docentes que utilizan herramientas como las guías docentes con el objetivo de saber cómo adaptar el trabajo según edades y sobre todo como hacer que los alumnos sientan un ambiente educativo óptimo. Por este motivo aumenta la cantidad de docentes impartiendo conocimientos a través de esta herramienta. Todo ello nos lleva a la conclusión de que el futuro pasa por la utilización de guías docentes y la interacción global con ellas. Por otro lado, nos encontramos con unas tasas de abandono escolar elevadas. Esta realidad social nos indica que el modelo educativo actual no está cumpliendo sus objetivos principales y no está consiguiendo una docencia eficaz y de calidad. De ello extraemos la conveniencia tanto de conocer las necesidades de los alumnos, como de que los docentes estén bien formados y preparados para impartir una docencia cualificada. Debido a esta necesidad de aportar a la sociedad información y apoyo para brindar una educación más eficaz, y aprovechando que las guías docentes aportan una visualización de como orientar a los profesores y que eso repercuta en una educación óptima para los alumnos, en el presente trabajo se propone la creación de una guía docente de estrategias para fomentar la motivación de las necesidades psicológicas básicas de los alumnos. Para conseguir ser directa la guía se basa en todas las estrategias a seguir para conseguir fomentar de una forma correcta la autonomía, la relación y la competencia de los alumnos y la implantación de cuatro supuestos prácticos por estrategia. Los cuatro supuestos prácticos se diferenciarán en la edad de los alumnos abordando desde Educación Primaria, Secundaria, Bachillerato, Formación profesional y Nivel universitario, creando así una herramienta docente que abarca todas las etapas escolares y con ejemplos de cada etapa escolar. Así conseguimos una herramienta con una gran valía y utilidad para los docentes de la disciplina de Educación Física en todas las edades docentes. Nowadays teaching is going through changes of great magnitude due to the modernization of the infrastructures and of the teaching tools, that try to offer a more efficient education for the students, and of more quality. In first place, it is expected that the academic achievement of the students increases, and that they have more interaction with the tools that the teacher offers. This is the case with the use of teaching guides that give the teacher a visualization of how to encourage learning with specific strategies that help students to engage and advance in the subject in an inclusive way. Today, more and more teachers are using tools such as teaching guides in order to know how to adapt work according to age and above all how to make students feel an optimal educational environment. This is why the number of teachers teaching through this tool is increasing. All this leads us to the conclusion that the future depends on the use of teaching guides and the global interaction with them. On the other hand, we have high dropout rates. This social reality tells us that the current educational model is not meeting its main objectives and is not achieving effective and quality teaching. From this we learn the convenience both of knowing the needs of the students, and of the fact that the teachers are well trained and prepared to give a qualified teaching. Because of this need to provide society with information and support for more effective education, and taking advantage of the fact that the teaching guides provide a direct visualization of how to guide teachers and that this has an impact on a more optimal education for students , This paper proposes the creation of a teaching guide on strategies to encourage motivation of the basic psychological needs of students. In order to be direct the guide is based on all the strategies to be followed in order to achieve a correct promotion of the autonomy, the relation and the competence of the students and the implementation of four practical assumptions per strategy. The four practical assumptions differ in age from the pupils by dealing with primary, secondary, secondary, vocational and university education, thus creating a teaching tool that covers all stages of school and with examples from each stage of school. In this way we obtain a tool with great value and usefulness for the teachers of the discipline of Physical Education in all the teaching ages.

Made available in DSpace on 2019-09-12T16:53:40Z (GMT). No. of bitstreams: 0 Previous issue date: 2019 The aim of this case report was to demonstrate the effects of the Maxillary Skeletal Expander (MSE) used to orthopedically correct a maxillary constriction, on the respiratory functions and swimming performance of a Para-athlete. Cone-beam computed tomography (CBCT) images taken before and after MSE activation were used to demonstrate the disarticulation of midpalatal suture, and the changes involved in dental and nasomaxillary structures, nasal cavity and pharyngeal airway. Respiratory tests included: maximum inspiratory and expiratory pressure, oral peak expiratory flow and inspiratory nasal flow. The 6-min-walk and heart rate recovery tests were also performed. Patient's swimming performances during national swimming competitions were compared. CBCT images showed that palatal expansion was 5.91 mm at the suture, and that nasal and pharyngeal airways increased in volume by 31%. All respiratory indices improved after MSE activation. The 6-min walk test and heart rate recovery test performance also improved after the maxillary expansion. Patient's swimming performance in all category were anemic prior to the treatment, but performance improved considerably after the expansion, particularly the 100 m-Backstroke modality. MSE treatment had a significant positive impact in respiratory functions and sport performance. (C) 2019 Elsevier Ltd. All rights reserved. [Garcez, Aguinaldo S.] Sao Leopoldo Mandic Inst & Res Ctr, Dept Microbiol, Campinas, SP, Brazil [Suzuki, Selly S.; Storto, Camilla J.] Sao Leopoldo Mandic Inst & Res Ctr, Dept Postgrad Orthodont, Campinas, SP, Brazil [Cusmanich, Karla G.] Universidade de Taubaté (Unitau), Dept Grad Phys Therapy [Elkenawy, Islam; Moon, Won] Univ Calif Los Angeles, Sch Dent, Sect Orthodont, Los Angeles, CA 90024 USA

Background: Diabetes has emerged as an epidemic in this country as well as worldwide. Increased oxidative stress and decreased antioxidant defense are established etiological factors of this multifactorial disease. Some of the recent studies reported deficiency of vitamin-D 3 in type-2 diabetic patients. Aims and Objectives: This study was aimed to estimate the total oxidative stress (TOS), the total antioxidant defense (TAD) and the plasma 25-hydroxy vitamin D 3 levels in patients of type-2 diabetes patients with an objective to elucidate if there is any significant correlation between the TOS, TAD and vitamin D 3 levels. Materials and Methods: The study was conducted in forty patients recently diagnosed type-2 diabetic and the findings were compared with age/sex matched healthy controls. Total oxidative stress and TAD values was estimated by two simple colorimetric tests developed and standardized in our laboratory, plasma 25-hydroxy vitamin D 3 by standardized ELISA method. Results and Discussion: The levels of vitamin D 3 in patients was found to be 50.17 ± 15.85ng/ml which was significantly decreased (P

The aim of the present study was to evaluate the primary stability of a two-miniscrew system inserted into a synthetic bone and to compare the system with the traditional one. Forty-five bi-layered polyurethane blocks were used to simulate maxillary cancellous and cortical bone densities. Samples were randomly assigned to three groups&mdash, one-miniscrew system (Group A, N = 23), two-miniscrew system (Group B, N = 22) and archwire-only (Group C, N = 10). A total of 67 new miniscrews were subdivided into Group A (23 singles) and Group B (22 couples). 30 mm of 19&Prime, &times, 25&Prime, archwires were tied to the miniscrew. The load was applied perpendicularly to the archwire. Maximum Load Value (MLV), Yield Load (YL) and Loosening Load (LL) were recorded for each group. The YL of Group B and C had a mean value respectively of 4.189 &plusmn, 0.390 N and 3.652 &plusmn, 0.064 N. The MLV of Group A, B and C had a mean value respectively of 1.871 &plusmn, 0.318N, of 4.843 &plusmn, 0.515 N and 4.150 &plusmn, 0.086 N. The LL of Group A and B had a mean value respectively of 1.871 &plusmn, 0.318 N and of 2.294 &plusmn, 0.333 N. A two- temporary anchorage device (TAD) system is on average stiffer than a one-TAD system under orthodontic loading.

Every living organism, from bacteria to humans, contains DNA encoding anything from a few hundred genes in intracellular parasites such as Mycoplasma, up to several tens of thousands in many higher organisms. The first observations indicating that the nucleus had some kind of organization were made over a hundred years ago. Understanding of its significance is both limited and aided by the development of techniques, in particular electron microscopy, fluorescence in situ hybridization, DamID and most recently HiC. As our knowledge about genome organization grows, it becomes apparent that the mechanisms are conserved in evolution, even if the individual players may vary. These mechanisms involve DNA binding proteins such as histones, and a number of architectural proteins, some of which are very much conserved, with some others having diversified and multiplied, acquiring specific regulatory functions. In this review we will look at the principles of genome organization in a hierarchical manner, from DNA packaging to higher order genome associations such as TADs, and the significance of radial positioning of genomic loci. We will then elaborate on the dynamics of genome organization during development, and how genome architecture plays an important role in cell fate determination. Finally, we will discuss how misregulation can be a factor in human disease.

Los modelos epistemológicos de referencia (MER en lo sucesivo) permiten incorporar a los problemas docentes la dimensión epistemológica. En el ámbito de la Teoría Antropológica de lo didáctico (TAD en lo sucesivo) la incorporación de esta dimensión es un paso obligado para definir el problema de investigación. Para su enseñanza-aprendizaje, la Geometría, al igual que el resto de saberes que se estudian en una institución escolar, sufre un proceso de transposición didáctica que modifica el saber sabio en saber a enseñar. Para estudiar el saber sabio, antes de que se transforme, el didacta debe reflexionar y explicitar cuál es su interpretación de ese saber matemático y justificar el porqué van a ser estudiados unos objetos matemáticos y no otros. En este trabajo se exponen los sistemas de referencia relativos que se han utilizado para la construcción de un MER para la enseñanza de la Geometría elemental del primer ciclo de secundaria y se detalla, a modo de ejemplo, una posible organización de las praxeologías que dicho MER aborda. 2016-17

Como contrapunto al monumentalismo tradicional en la enseñanza de las obras matemáticas, la teoría antropológica de lo didáctico (TAD) propone el paradigma del cuestionamiento del mundo, siendo los recorridos de estudio e investigación (REI) los dispositivos que propone para implementarlo en las instituciones escolares. Sin embargo, esta implantación del nuevo paradigma encuentra restricciones, en particular de índole metodológica. En el presente trabajo presentamos una propuesta para posibilitar la supervivencia de los REI en una institución con una metodología basada en el aprendizaje cooperativo, y analizamos cómo los REI y el aprendizaje cooperativo pueden complementarse. 2020-21

Trabajo fin de máster. Defendido en diciembre de 2018. El objetivo de este estudio retrospectivo fue determinar la tasa de fracaso de los minitornillos colocados en pacientes de ortodoncia en el Hospital San Rafael entre el año 2013 y 2018. Material y métodos. Se evaluaron 100 minitornillos colocados en 63 pacientes de ortodoncia. Las variables estudiadas se clasificaron como (1) factores relacionados con el paciente: edad, sexo y patrón esquelético craneofacial; (2) Factores relacionados con la ubicación: hueso (maxilar o mandíbula) y área; (3) Indicación de TAD (intrusión / retrusión con anclaje máximo, tracción canina ...). En estas comparaciones, se utilizó la prueba t de Student en variables dicotómicas y el test ANOVA en variables con más de 2 categorías. El análisis de supervivencia se realizó mediante la técnica de Kaplan Meier y el tiempo de supervivencia se comparó de acuerdo con diferentes variables con la prueba Log Rank (Mantel-Cox). Mediante el test de chi-cuadrado, se estudió una asociación entre la ubicación (maxilar / mandíbula) y la forma de fracaso del minitornillo. En todas las comparaciones, se utilizó un nivel de significación de α = 0.05 (error de tipo I) y una potencia estadística de 0.80 (error de tipo II = 0.20). El análisis se realizó con SPSS V22. Resultados: Se observó una tasa de fracaso del 18%. No hubo diferencias estadísticamente significativas en el fracaso en cuanto al sexo, edad, patrón craneofacial y localización (maxilar / mandíbula) o área (p˃0.05). Conclusión: La tasa de fracaso en la inserción de minitornillos (18%) es semejante a la de otros estudios. El uso de minitornillos supone un método eficaz de anclaje facilitando la mecánica ortodóncica. El sexo, la edad, el patrón craneofacial y la localización no parecen desempeñar un factor de riesgo en la estabilidad del minitornillo, si bien los datos obtenidos apuntan en la misma dirección que los encontrados en otros estudios. Abstract: The purpose of this retrospective study was to determine the failure rate of miniscrews placed in orthodontic patients at San Rafael Hospital between 2013 and 2018 (Madrid). Subject: Based on previous studies we expect to find a failure rate of around 15%, assuming an accuracy of 7% and a confidence level (1-α) = 95%, a sample of 100 mini-screws will be required. So, 100 miniscrew placed in 63 orthodontic patients were evaluated. The variables studied were classified as (1) patient-related factors: age, sex and craniofacial skeletal pattern; (2) location-related factors: bone (maxilla or mandible) and area, (3) TADs-indication (intrusion/ retrusion with maximum anchorage, canine traction...) In these comparisons, the Student t test was used in dichotomous variables and the one-way ANOVA test in variables with more than 2 categories. The survival analysis was performed using the Kaplan Meier technique and the survival time was compared according to different variables with the Log Rank test (Mantel-Cox). By means of the chi-square test, an association between the location (maxillary / mandible) and the causes of the failure of the mini-screw was studied. In all comparisons, a significance level of α = 0.05 (type I error) and a statistical power of 0.80 (type II error = 0.20) were used. The analysis has been done with SPSS V22. Results: A total failure rate of 18% was observed. There was no statistically significant difference in failure regarding sex, age, facial pattern or location (maxilla or mandible) or area (p˃0.05). Conclusion: 18% failure rate is consistent with previous studies. Sex, age, craniofacial pattern and location do not seem to play a role in success of miniscrew stability. Ordenador con navegador de Internet ; Adobe Acrobat Reader 84 p. (Según el contador de la aplicación)

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.

Background The transcriptional activation of HoxD genes during mammalian limb development involves dynamic interactions with two topologically associating domains (TADs) flanking the HoxD cluster. In particular, the activation of the most posterior HoxD genes in developing digits is controlled by regulatory elements located in the centromeric TAD (C-DOM) through long-range contacts. Results To assess the structure–function relationships underlying such interactions, we measured compaction levels and TAD discreteness using a combination of chromosome conformation capture (4C-seq) and DNA FISH. We assessed the robustness of the TAD architecture by using a series of genomic deletions and inversions that impact the integrity of this chromatin domain and that remodel long-range contacts. We report multi-partite associations between HoxD genes and up to three enhancers. We find that the loss of native chromatin topology leads to the remodeling of TAD structure following distinct parameters. Conclusions Our results reveal that the recomposition of TAD architectures after large genomic re-arrangements is dependent on a boundary-selection mechanism in which CTCF mediates the gating of long-range contacts in combination with genomic distance and sequence specificity. Accordingly, the building of a recomposed TAD at this locus depends on distinct functional and constitutive parameters. Electronic supplementary material The online version of this article (doi:10.1186/s13059-017-1278-z) contains supplementary material, which is available to authorized users.

The nuclear lamina (NL) is a meshwork of lamins and lamin-associated proteins adjoining the inner side of the nuclear envelope. In early embryonic cells, the NL mainly suppresses background transcription, whereas, in differentiated cell types, its disruption affects gene expression more severely. Normally, the NL serves as a backbone for multiple chromatin anchoring sites, thus shaping the spatial organization of chromosomes in the interphase nucleus. However, upon cell senescence, aging, or in some types of terminally differentiated cells and lamin-associated diseases, the loss of NL-chromatin tethering causes drastic alterations in chromosome architecture. Here, we provide an overview of the recent advances in the field of NL-chromatin interactions, focusing on their impact on chromatin positioning, compaction, repression, and spatial organization.

Acemel, Rafael D. et al., The HoxA and HoxD gene clusters of jawed vertebrates are organized into bipartite three-dimensional chromatin structures that separate long-range regulatory inputs coming from the anterior and posterior Hox-neighboring regions. This architecture is instrumental in allowing vertebrate Hox genes to pattern disparate parts of the body, including limbs. Almost nothing is known about how these three-dimensional topologies originated. Here we perform extensive 4C-seq profiling of the Hox cluster in embryos of amphioxus, an invertebrate chordate. We find that, in contrast to the architecture in vertebrates, the amphioxus Hox cluster is organized into a single chromatin interaction domain that includes long-range contacts mostly from the anterior side, bringing distant cis-regulatory elements into contact with Hox genes. We infer that the vertebrate Hox bipartite regulatory system is an evolutionary novelty generated by combining ancient long-range regulatory contacts from DNA in the anterior Hox neighborhood with new regulatory inputs from the posterior side., Work was funded by grants from the Ministerio de Economía y Competitividad (BFU2013-41322-P to J.L.G.-S.; Juan de la Cierva postdoctoral contract to I.M.; BFU2014-58449-JIN to J.J.T.); the Andalusian government (BIO-396 to J.L.G.-S.; C2A (EE: 2013/2506) to D.P.D. and I.I.-A.); the European Research Council (ERC; grant 268513) to P.W.H.H. and F.M.; a European Molecular Biology Organization (EMBO) short fellowship to I.M.; the Universidad Pablo de Olavide to J.J.T.; and Conicyt 'Becas Chile' to D.A.

Background Orthodontic protraction of mandibular molars without maxillary counterbalance extraction in cases of aplasia or extraction requires stable anchorage. Reinforcement may be achieved by using either temporary anchorage devices (TAD) or a fixed, functional appliance. The objective was to compare the clinical effectiveness of both methods by testing the null-hypothesis of no significant difference in velocity of space closure (in mm/month) between them. In addition, we set out to describe the quality of posterior space management and treatment-related factors, such as loss of anchorage (assessed in terms of proportions of gap closure by posterior protraction or anterior retraction), frequencies of incomplete space closure, and potential improvement in the sagittal canine relationship. Methods Twenty-seven subjects (15 male/12 female) with a total of 36 sites treated with a lingual multi-bracket appliance were available for retrospective evaluation of the effects of anchorage reinforcement achieved with either a Herbst appliance (nsubjects = 15; 7 both-sided/8 single-sided Herbst appliances; nsites = 22) or TADs (nsubjects = 12; 2 both-sided; 10 single-sided; nsites = 14). Descriptive analysis was based on measurements using intra-oral photographs which were individually scaled to corresponding plaster casts and taken on insertion of anchorage mechanics (T1), following removal of anchorage mechanics (T2), and at the end of multi-bracket treatment (T3). Results The null-hypothesis was rejected: The rate of mean molar protraction was significantly faster in the Herbst-reinforced group (0.51 mm/month) than in the TAD group (0.35). While complete space closure by sheer protraction of posterior teeth was achieved in all Herbst-treated cases, space closure in the TAD group was achieved in 76.9 % of subjects by sheer protraction of molars, and it was incomplete in 50 % of cases (mean gap residues: 1 mm). Whilst there was a deterioration in the canine relationship towards Angle-Class II malocclusion in 57.14 % of space closure sites in TAD-treated subjects (indicating a loss of anchorage), an improvement in canine occlusion was observed in 90.9 % of Herbst-treated cases. Conclusion Subjects requiring rapid space closure by molar protraction in combination with a correction of distal occlusion may benefit from using Herbst appliances for anterior segment anchorage reinforcement rather than TAD anchorage. peerReviewed

Background Hafnia alvei is an opportunistic pathogen involved in various types of nosocomical infections. The species has been found to inhabit food and mammalian guts. However, its status as an enteropathogen, and whether the food-inhabiting strains could be a source of gastrointestinal infection remains obscure. In this report we present a draft genome of H. alvei strain FB1 isolated from fish paste meatball, a food popular among Malaysian and Chinese populations. The data was generated on the Illumina MiSeq platform. Results A comparative study was carried out on FB1 against two other previously sequenced H. alvei genomes. Several gene clusters putatively involved in survival and pathogenesis of H. alvei FB1 in food and gut environment were characterised in this study. These include the widespread colonisation island (WCI), the tad locus that is known to play an essential role in biofilm formation, a eut operon that might contribute to advantage in nutrient acquisition in gut environment, and genes responsible for siderophore production This features enable the bacteria to successful colonise in the host gut environment. Conclusion With the whole genome data of H. alvei FB1 presented in this study, we hope to provide an insight into future studies on this candidate of enteropathogen by looking into the possible mechanisms employed to survive stresses and gain advantage in competitions, which eventually leads to successful colonisation and pathogenesis. This is to serve as the basis for more effective clinical diagnosis and treatment.

Anchorage is one of the most important elements for successful orthodontic treatment. Traditionally, orthodontics employed teeth and extraoral or intraoral appliances for anchorage, often relying on the patient compliance for its effectiveness. Osseointegrated dental implants were introduced to strengthen anchorage (Wehrbein and Merz, 1998; Wehrbein et al ., 1999; Chen et al ., 2005; Wehrbein and Gollner, 2007), but these implants present with a number of disadvantages that limit routine use. More recently, different types of skeletal anchorage devices have been introduced, offering potential advantages compared with osseointegrated implants, including: smaller size, which in turn allows more versatile use and reduces amount of surgical intervention necessary, resulting in less patient discomfort; the possibility of immediate loading; lower costs; and ease of removal. Mini-implants are derived from endosseous implants. They have a conical shape with a head that emerges from the mucosa and that allows connection with orthodontic appliances; mini-implants also contain a smooth transmucosal neck and an endosseous threaded body that can be manufactured with different thread designs and body shapes. Length and diameter vary widely between makes, and the surface is generally smooth, which limits osseointegration. Mini-plates that are used for orthodontic anchorage are very similar to maxillofacial plates, consisting of a base-plate and fixation screws made of titanium. The shape and size can differ, and the number of fixations can vary from two to five screws. Mini-screws are made of titanium and are specifically designed for orthodontic anchorage. Their shape is similar to that of mini-implants, but mini-screws are usually smaller (less than 2mm in diameter) and sometimes more tapered. The thread can be self-drilling to allow direct insertion without the use of pre-drilling, which simplifies the insertion technique. To encompass all of the above-mentioned devices in one definition, we decided to use the term …

A rapid and sensitive HPLC-RP method for simultaneous determination of tiazofurin, its 5'-O acetyl and benzoyl esters and their active metabolite thiazole-4-carboxamide adenine dinucleotide was developed and validated. The method allowed determination and quantification of nanomolar quantities of these substances in cell extracts of treated cells, and was also used in kinetic studies of cellular uptake of tiazofurin and its esters from the cultivation medium. Separation of the analyzed substances from unidentified peaks from both biological materials was achieved by gradient elution, thus reducing the possibility of interference. The mobile phase consisted of a 0.1 M sodium-hydrogen phosphate, pH 5.1 and methanol. Run time was 22 min, with 5 min equilibration time. (C) 2002 Elsevier Science B.V. All rights reserved.

Background Unstable proximal femoral fractures are common and challenging for the orthopaedic surgeon. Often, these are treated with intramedullary nails. The most common mode of failure of any device to treat these fractures is cut-out. The Synthes proximal femoral nail antirotation (PFNA) is unique because it is the only proximal femoral intramedullary nail which employs a helical blade in lieu of a lag screw. The optimal tip-apex distance is 25 mm or less for a dynamic hip screw. The optimal blade tip placement is not known for the PFNA. Aim The aim of this study is to determine if the traditional tip-apex distance rule (

Anchorage control has been the main stay of orthodontic therapy. Mini implants have provided with an excellent solution to harness skeletal anchorage. Use of mini implants is preferred for their versatile applications, but the main issue if for deciding the position of the implant placement. Specific guidelines have to be followed for correct implant placement. In this clinical innovation we have designed a chair side jig for mini implant placement which is easy to fabricate and apply.

Dr. Jay Bowman is a renowned clinician and speaker all across the world. APOS Trends in an exclusive conversation with him discusses his tryst with Micro Implant Anchorage.

Se presenta en este artículo una propuesta para el desarrollo de programas eficientes en el marco de la programación con tipos abstractos de datos (TAD), con el objetivo de respetar la estructura modular de los programas propia de este ámbito. La propuesta se centra en el concepto de atajo como camino eficiente de acceso a los datos, alternativo al acceso mediante las operaciones propias del TAD, y se desarrolla sobre un TAD concreto, el almacén de elementos. La definición de los atajos es altamente formal, mediante especificaciones algebraicas interpretadas con semántica inicial, de manera que el resultado tiene un significado bien definido y encaja sin problemas en el marco de la programación con TAD. La eficiencia se asegura mediante una implementación adecuada del tipo, que proporciona acceso constante a los datos siguiendo los atajos sin penalizar las otras operaciones del TAD. Se ilustra la utilidad de la propuesta mediante un ejemplo concreto.

International audience; Vertebrate Hox genes encode transcription factors operating during the development of multiple organs and structures. However, the evolutionary mechanism underlying this remarkable pleiotropy remains to be fully understood. Here, we show that Hoxd8 and Hoxd9, two genes of the HoxD complex, are transcribed during mammary bud (MB) development. However, unlike in other developmental contexts, their coexpression does not rely on the same regulatory mechanism. Hoxd8 is regulated by the combined activity of closely located sequences and the most distant telomeric gene desert. On the other hand, Hoxd9 is controlled by an enhancer-rich region that is also located within the telomeric gene desert but has no impact on Hoxd8 transcription, thus constituting an exception to the global regulatory logic systematically observed at this locus. The latter DNA region is also involved in Hoxd gene regulation in other contexts and strongly interacts with Hoxd9 in all tissues analyzed thus far, indicating that its regulatory activity was already operational before the appearance of mammary glands. Within this DNA region and neighboring a strong limb enhancer, we identified a short sequence conserved in therian mammals and capable of enhancer activity in the MBs. We propose that Hoxd gene regulation in embryonic MBs evolved by hijacking a preexisting regulatory landscape that was already at work before the emergence of mammals in structures such as the limbs or the intestinal tract.

La présente étude vise à déterminer l’opportunité de lancer une offre complémentaire de transports publics dédiée sous forme de transports à la demande (TAD) dans l’Agglomération de Fribourg. Cette étude est une aide à la décision pour l’Agglomération. Elle doit lui permettre de statuer sur la suite à donner et, le cas échéant, d’identifier les démarches et investigations encore nécessaires en vue du déploiement d’une offre TAD. L’étude repose sur l’analyse de trois des formes usuelles du transport à la demande : le TAD en complément spatial, le TAD en complément horaire et le TAD pour des publics-cibles. Les analyses menées consistent en une présentation de benchmark, des revues de littérature, ainsi que des analyses spatiales, quantitatives et qualitatives (focus-groupes et entretiens). Tout au long de l’étude, des contacts ont été pris et des entretiens ont été réalisés avec des experts ou des responsables d’offres TAD existantes. Ce premier travail a permis de faire émerger six offres possibles :  Un TAD comme nouvelle offre en zone périurbaine ou rurale  Un TAD pour le premier et le dernier kilomètre  Un TAD de complément pour les heures creuses  Un TAD urbain nocturne  Un TAD pendulaire nocturne  Un TAD pour les personnes âgées Ces six offres ont été décrites de manière systématique pour rendre compte des territoires et publics concernés, des formes de déploiement TAD et des véhicules qui peuvent permettre d’assurer le service et finalement de l’organisation temporelle et des modalités de réservation. Une synthèse sous forme d’analyse Forces/Faiblesses/Opportunités/Menaces facilite la lecture transversale des enseignements. Ces éléments ont été les supports de discussion d’une séance de pilotage qui s’est déroulée le 4 mai 2021 à Fribourg. Quatre perspectives d’offres ont été retenue : (1) le transport à la demande dans les territoires peu ou pas desservis, (2) le transport à la demande pendulaire nocturne, (3) le transport à la demande « dernier train » et (4) le transport à la demande pour les personnes âgées. Ces quatre offres ont fait l’objet d’une analyse complémentaire devant permettre à l’Agglomération de Fribourg d’arbitrer sur la suite éventuelle à donner et la forme de celle-ci.