664 research outputs found
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
The Shortest Telomere, Not Average Telomere Length, Is Critical for Cell Viability and Chromosome Stability
Loss of telomere function can induce cell cycle arrest and apoptosis. To investigate the processes that trig- ger cellular responses to telomere dysfunction, we crossed mTR/ G6 mice that have short telomeres with mice heterozygous for telomerase (mTR/) that have long telomeres. The phenotype of the telomerase null offspring was similar to that of the late generation parent, although only half of the chromosomes were short. Strikingly, spectral karyotyping (SKY) analysis revealed that loss of telomere function occurred pref- erentially on chromosomes with critically short telo- meres. Our data indicate that, while average telomere length is measured in most studies, it is not the aver- age but rather the shortest telomeres that constitute telomere dysfunction and limit cellular survival in the absence of telomerase
The Shortest Telomere, Not Average Telomere Length, Is Critical for Cell Viability and Chromosome Stability
Loss of telomere function can induce cell cycle arrest and apoptosis. To investigate the processes that trig- ger cellular responses to telomere dysfunction, we crossed mTR/ G6 mice that have short telomeres with mice heterozygous for telomerase (mTR/) that have long telomeres. The phenotype of the telomerase null offspring was similar to that of the late generation parent, although only half of the chromosomes were short. Strikingly, spectral karyotyping (SKY) analysis revealed that loss of telomere function occurred pref- erentially on chromosomes with critically short telo- meres. Our data indicate that, while average telomere length is measured in most studies, it is not the aver- age but rather the shortest telomeres that constitute telomere dysfunction and limit cellular survival in the absence of telomerase
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
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Ancestral Mutation in Telomerase Causes Defects in Repeat Addition Processivity and Manifests As Familial Pulmonary Fibrosis
The telomerase reverse transcriptase synthesizes new telomeres onto chromosome ends by copying from a short template within its integral RNA component. During telomere synthesis, telomerase adds multiple short DNA repeats successively, a property known as repeat addition processivity. However, the consequences of defects in processivity on telomere length maintenance are not fully known. Germline mutations in telomerase cause haploinsufficiency in syndromes of telomere shortening, which most commonly manifest in the age-related disease idiopathic pulmonary fibrosis. We identified two pulmonary fibrosis families that share two non-synonymous substitutions in the catalytic domain of the telomerase reverse transcriptase gene hTERT: V791I and V867M. The two variants fell on the same hTERT allele and were associated with telomere shortening. Genealogy suggested that the pedigrees shared a single ancestor from the nineteenth century, and genetic studies confirmed the two families had a common founder. Functional studies indicated that, although the double mutant did not dramatically affect first repeat addition, hTERT V791I-V867M showed severe defects in telomere repeat addition processivity in vitro. Our data identify an ancestral mutation in telomerase with a novel loss-of-function mechanism. They indicate that telomere repeat addition processivity is a critical determinant of telomere length and telomere-mediated disease
Short Telomeres in Hatchling Snakes: Erythrocyte Telomere Dynamics and Longevity in Tropical Pythons
Telomere length (TL) has been found to be associated with life span in birds and humans. However, other studies have demonstrated that TL does not affect survival among old humans. Furthermore, replicative senescence has been shown to be induced by changes in the protected status of the telomeres rather than the loss of TL. In the present study we explore whether age- and sex-specific telomere dynamics affect life span in a long-lived snake, the water python (Liasis fuscus)
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 incluÃdos 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 plantÃgrados e foram submetidos à avaliação clÃnica e radiográfica, seguido pelo exame de ultrassom Doppler colorido (UDC), visando a identificação das artérias tibiais anterior e posterior na altura do tornozelo. O nÃvel 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 clÃnico da correção do PTC, maior foi o calibre da artéria tibial anterior.UNIFESP Departamento de Ortopedia e TraumatologiaUNIFESP, Depto. de Ortopedia e TraumatologiaSciEL
Telomere shortening and mitotic dysfunction generate cytogenetic heterogeneity in a subgroup of renal cell carcinomas
Massively Parallel RNA Chemical Mapping with a Reduced Bias MAP-seq Protocol
Chemical mapping methods probe RNA structure by revealing and leveraging
correlations of a nucleotide's structural accessibility or flexibility with its
reactivity to various chemical probes. Pioneering work by Lucks and colleagues
has expanded this method to probe hundreds of molecules at once on an Illumina
sequencing platform, obviating the use of slab gels or capillary
electrophoresis on one molecule at a time. Here, we describe optimizations to
this method from our lab, resulting in the MAP-seq protocol (Multiplexed
Accessibility Probing read out through sequencing), version 1.0. The protocol
permits the quantitative probing of thousands of RNAs at once, by several
chemical modification reagents, on the time scale of a day using a table-top
Illumina machine. This method and a software package MAPseeker
(http://simtk.org/home/map_seeker) address several potential sources of bias,
by eliminating PCR steps, improving ligation efficiencies of ssDNA adapters,
and avoiding problematic heuristics in prior algorithms. We hope that the
step-by-step description of MAP-seq 1.0 will help other RNA mapping
laboratories to transition from electrophoretic to next-generation sequencing
methods and to further reduce the turnaround time and any remaining biases of
the protocol.Comment: 22 pages, 5 figure
A universal telomerase RNA core structure includes structured motifs required for binding the telomerase reverse transcriptase protein
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