Tetrahymena telomerase catalyzes nucleolytic cleavage and nonprocessive elongation

Telomerase is a ribonucleoprotein enzyme that adds telomeric repeats to chromosomes, maintaining telomere length and stabilizing chromosome ends. In vitro, telomerase from the ciliate Tetrahymena elongates single-stranded, guanosine-rich DNA primers by adding repeats of the Tetrahymena telomeric sequence, dT2G4. We have identified two activities of Tetrahymena telomerase in addition to the previously described processive elongation reaction: a 3'-5' nucleolytic cleavage of primer or product DNA and a nonprocessive mode of elongation. The nucleolytic cleavage activity removed residues not conforming to the telomeric repeat sequence from a primer 3' end, eliminating mismatch between DNA primer and RNA template sequences. Template-matched residues were also cleaved from primer or product DNA. Specific primer lengths, sequences, and concentrations stimulated cleavage and processive or nonprocessive elongation differentially. These newly identified activities suggest that telomerase may catalyze a range of telomere synthesis and repair functions and suggest mechanistic similarities between telomerase and RNA polymerase enzymes. On the basis of our results, we propose a model for telomerase primer binding, cleavage, and elongation

Leadership, the logic of sufficiency and the sustainability of education

The notion of sufficiency has not yet entered mainstream educational thinking, and it still has to make its mark upon educational leadership. However, a number of related concepts – particularly those of sustainability and complexity theory – are beginning to be noticed. This article examines these two concepts and uses them to critique the quasi-economic notion of efficiency, before arguing that the concept of sufficiency arises naturally from this discussion. This concept, originally derived from environmental thinking, has both metaphorical and practical impact for educational organizations and their leadership. An examination of three possible meanings suggests that while an embrace of an imperative concept of sufficiency seems increasingly necessary, its adoption would probably lead to a number of other problems, as it challenges some fundamental societal values and assumptions. Nevertheless, the article argues that these need to be addressed for the sake of both sustainable leadership and a sustainable planet

A Collaborative Approach to Developing Culturally Themed Digital Collections

The College of Arts and Sciences at the University of Kentucky (UK) has created the Passport to the World Program (PWP) to celebrate campus-wide the cultural heritage of a country or region every academic year. The UK Libraries International Programs has been an active contributor to PWP by collaborating with faculty and different library departments to develop unique digital collections that serve to connect viewers with the featured country or region. To begin with, the Director of the International Programs (DIP) consults faculty and librarians at the UK Libraries Special Collections Research Center to select relevant materials for digitization. She also sources interesting artifacts from the larger community to create compilations of digital photos. Afterward, DIP invites faculty to annotate the images in order to highlight the cultural and historical significance of the materials and artifacts. The images, their annotations, and the accompanying metadata are ingested into UK’s institutional repository to create a virtual exhibit that is freely accessible online. At the same time, a corresponding physical exhibit is set up in the library to showcase the images. People interested in learning more about the images can scan QR codes to view the virtual exhibit, read the annotations, and download the images. Since the institutional repository tracks download rates of available items, faculty who have contributed to the virtual exhibit receive periodical notifications of the download counts of the images. The repository platform also offers an online dashboard for DIP and the faculty to assess the page hits of the virtual exhibit and to analyze the geographical and institutional distributions of the downloads. As part of the repository holdings, the virtual exhibit is preserved through the library’s participation in the Digital Preservation Network. This presentation demonstrates that the library can play a significant role in supporting a campus-wide initiative by leveraging its resources and services to build, assess, and preserve culturally themed digital collections. The outcome not only helps promote the awareness of a foreign culture but also increases the visibility of some little-known artifacts and rare library materials

A Collaborative Approach to Developing Culturally Themed Digital Collections

The College of Arts and Sciences at the University of Kentucky (UK) has created the Passport to the World Program (PWP) to celebrate campus-wide the cultural heritage of a country or region every academic year. The UK Libraries International Programs has been an active contributor to PWP by collaborating with faculty and different library departments to develop unique digital collections that serve to connect viewers with the featured country or region. To begin with, the Director of the International Programs (DIP) consults faculty and librarians at the UK Libraries Special Collections Research Center to select relevant materials for digitization. She also sources interesting artifacts from the larger community to create compilations of digital photos. Afterward, DIP invites faculty to annotate the images in order to highlight the cultural and historical significance of the materials and artifacts. The images, their annotations, and the accompanying metadata are ingested into UK’s institutional repository to create a virtual exhibit that is freely accessible online. At the same time, a corresponding physical exhibit is set up in the library to showcase the images. People interested in learning more about the images can scan QR codes to view the virtual exhibit, read the annotations, and download the images. Since the institutional repository tracks download rates of available items, faculty who have contributed to the virtual exhibit receive periodical notifications of the download counts of the images. The repository platform also offers an online dashboard for DIP and the faculty to assess the page hits of the virtual exhibit and to analyze the geographical and institutional distributions of the downloads. As part of the repository holdings, the virtual exhibit is preserved through the library’s participation in the Digital Preservation Network. This presentation demonstrates that the library can play a significant role in supporting a campus-wide initiative by leveraging its resources and services to build, assess, and preserve culturally themed digital collections. The outcome not only helps promote the awareness of a foreign culture but also increases the visibility of some little-known artifacts and rare library materials

Angular Dependence of Neutrino Flux in KM3 Detectors in Low Scale Gravity Models

Cubic kilometer neutrino telescopes are capable of probing fundamental questions of ultra-high energy neutrino interactions. There is currently great interest in neutrino interactions caused by low-scale, extra dimension models. Above 1 PeV the cross section in low scale gravity models rises well above the total Standard Model cross section. We assess the observability of this effect in the 1 PeV - 100 PeV energy range of kilometer-scale detectors with several new points of emphasis that hinge on enhanced neutral current cross sections. A major point is the importance of ``feed-down'' regeneration of upward neutrino flux, driven by new-physics neutral current interactions in the flux evolution equations. Feed-down is far from negligible, and it is essential to include its effect. We then find that the angular distribution of events has high discriminating value in separating models. In particular the ``up-to-down'' ratio between upward and downward-moving neutrino fluxes is a practical diagnostic tool which can discriminate between models in the near future. The slope of the angular distribution, in the region of maximum detected flux, is also substantially different in low-scale gravity and the Standard Model. These observables are only weakly dependent on astrophysical flux uncertainties. We conclude that angular distributions can reveal a breakdown of the Standard Model and probe the new physics beyond, as soon as data become available.Comment: 25 pages, 6 figures, discussion of calculations expanded, references adde

Evaluation of arterial anatomy in congenital clubfoot with color doppler ultrasound

OBJECTIVE: This investigation intended to evaluate anterior and posterior tibial arteries at the ankle joint level in congenital clubfoot, by using color Doppler ultrasound (CDU). MATERIAL AND METHOD: Twenty patients with idiopathic clubfoot were selected, from which 18 had unilateral involvement and two had bilateral involvement. Of the 18 patients with unilateral clubfoot, 16 went through surgical treatment and the other two were submitted to conservative treatment with serial casting. Of the bilateral cases, one patient was treated surgically and the other was treated with serial casting. All patients were clinically and radiographically assessed. We used the functional rating as described by Lehman. Then, CDU was applied bilaterally at the ankle joint level, trying to identify both posterior and anterior tibial arteries. RESULTS: In our present series of 20 cases with idiopathic clubfoot, in just one patient we could not identify the anterior tibial artery at the ankle joint level. In 12 patients who have had their arterial flow speeds and diameters measured by UDC, a positive correlation was found between functional level and anterior tibial artery diameter. No statistically significant differences were found between both flow speed and diameter of anterior tibial artery of the normal side, when compared to the affected side (in patients with unilateral disease). CONCLUSION: In our sample, we could not find any significant differences in arterial morphology and flow speed between the normal and the affected side. Furthermore, we noticed that the better the clinical result of clubfoot correction, the larger the diameter of anterior tibial artery in affected feet.OBJETIVO: Avaliação ultrassonográfica das artérias tibial anterior e posterior no pé torto congênito (PTC). MATERIAL E MÉTODO: Foram incluídos 20 pacientes portadores de PTC idiopático compreendendo 18 casos unilaterais e dois bilaterais, sendo que 17 pacientes foram submetidos a tratamento cirúrgico e três a tratamento conservador. Todos os pacientes apresentavam pés plantígrados e foram submetidos à avaliação clínica e radiográfica, seguido pelo exame de ultrassom Doppler colorido (UDC), visando a identificação das artérias tibiais anterior e posterior na altura do tornozelo. O nível funcional foi classificado pelos critérios de Lehman. RESULTADOS: Nesta série de 20 pacientes, somente em um não foi identificada a artéria tibial anterior. Nos 12 pacientes submetidos à mensuração de fluxo e calibre pelo UDC, foi encontrada uma correlação positiva entre o grau funcional do PTC e o calibre da artéria tibial anterior. Não houve redução estatisticamente significante entre o fluxo e calibre da artéria tibial anterior do lado normal em comparação com o lado alterado (nos casos de doença unilateral). CONCLUSÕES: Não houve alteração significativa da morfologia e fluxo arterial quando comparamos os lados afetado e normal. Além disso, quanto melhor o resultado clínico da correção do PTC, maior foi o calibre da artéria tibial anterior.UNIFESP Departamento de Ortopedia e TraumatologiaUNIFESP, Depto. de Ortopedia e TraumatologiaSciEL

Telomerase activity and telomere length in primary and metastatic tumors from pediatric bone cancer patients

The presence of telomerase activity has been analyzed in almost all tumor types and tumor-derived cell lines. However, there are very few studies that focus on the presence of telomerase activity in bone tumors, and most of them report analysis on very few samples or bone-derived cell lines. The objective of this study was to analyze the telomere length and telomerase activity in primary tumors and metastatic lesions from pediatric osteosarcoma and Ewing's sarcoma patients. The presence of telomerase activity was analyzed by the telomeric repeat amplification protocol assay, and the telomere length was measured by Southern blot. Results were related to survival and clinical outcome. Telomerase activity was detected in 85% of the bone tumor metastases (100% Ewing's sarcomas and 75% osteosarcomas) but only in 12% of the primary tumors (11.1% osteosarcomas and 12.5% Ewing's sarcomas). Bone tumor tissues with telomerase activity had mean telomere lengths 3 kb shorter than those with no detectable telomerase activity (p = 0.041). The presence of telomerase activity was associated with survival (p = 0.009), and longer event-free survival periods were found in patients who lacked telomerase activity compared with those who had detectable telomerase activity levels in their tumor tissues (p = 0.037). The presence of longer telomeres in primary pediatric bone tumors than in metastases could be indicative of alternative mechanisms of lengthening of telomeres for their telomere maintenance rather than telomerase activity. Nevertheless, the activation of telomerase seems to be a crucial step in the malignant progression and acquisition of invasive capability of bone tumors

Going Global: The Library as a Critical Player in Internationalizing a University

To support the University of Kentucky’s (UK) strategic plan, UK Libraries created a Director of International Programs (DIP) position in 2010 to plan and manage its international initiatives. In consultation of the UK administration, the DIP identified areas in which the library could make major contributions toward internationalization. The DIP has made significant progress in the areas by participating in the College of Arts and Sciences’ Passport to the World Program. Each year the College celebrates the cultural heritage of a country/region. The DIP and liaison librarians collaborate with faculty from different departments to annotate and showcase relevant materials from the library’s special collections in physical and online exhibits. We also host lectures and movie screenings in which faculty introduce audiences to specific cultural features and practices. Assessment of the events is reported to the Provost’s Office annually. Thanks to positive feedback and faculty recommendations, the library’s involvement in the Passport to the World Program went from peripheral in 2010 to being a major organizer with the appointment of the DIP as a member of the Program’s steering committee in 2013. Meanwhile, the annual library budget for hosting international events jumped from a pittance to $8,000. This poster demonstrates using images and brochures that the library has been a crucial player in executing UK’s internationalization strategy. Liaison librarians have (and will continue to) played a pivotal role in building lasting relationships with various campus constituents to support UK’s strategic goals

Mechanisms of human telomerase reverse transcriptase (hTERT) regulation: clinical impacts in cancer

Background Limitless self-renewal is one of the hallmarks of cancer and is attained by telomere maintenance, essentially through telomerase (hTERT) activation. Transcriptional regulation of hTERT is believed to play a major role in telomerase activation in human cancers. Main body The dominant interest in telomerase results from its role in cancer. The role of telomeres and telomere maintenance mechanisms is well established as a major driving force in generating chromosomal and genomic instability. Cancer cells have acquired the ability to overcome their fate of senescence via telomere length maintenance mechanisms, mainly by telomerase activation. hTERT expression is up-regulated in tumors via multiple genetic and epigenetic mechanisms including hTERT amplifications, hTERT structural variants, hTERT promoter mutations and epigenetic modifications through hTERT promoter methylation. Genetic (hTERT promoter mutations) and epigenetic (hTERT promoter methylation and miRNAs) events were shown to have clinical implications in cancers that depend on hTERT activation. Knowing that telomeres are crucial for cellular self-renewal, the mechanisms responsible for telomere maintenance have a crucial role in cancer diseases and might be important oncological biomarkers. Thus, rather than quantifying TERT expression and its correlation with telomerase activation, the discovery and the assessment of the mechanisms responsible for TERT upregulation offers important information that may be used for diagnosis, prognosis, and treatment monitoring in oncology. Furthermore, a better understanding of these mechanisms may promote their translation into effective targeted cancer therapies. Conclusion Herein, we reviewed the underlying mechanisms of hTERT regulation, their role in oncogenesis, and the potential clinical applications in telomerase-dependent cancers.info:eu-repo/semantics/publishedVersio