70 research outputs found

    G4 motifs correlate with promoter-proximal transcriptional pausing in human genes

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    The RNA Pol II transcription complex pauses just downstream of the promoter in a significant fraction of human genes. The local features of genomic structure that contribute to pausing have not been defined. Here, we show that genes that pause are more G-rich within the region flanking the transcription start site (TSS) than RefSeq genes or non-paused genes. We show that enrichment of binding motifs for common transcription factors, such as SP1, may account for G-richness upstream but not downstream of the TSS. We further show that pausing correlates with the presence of a GrIn1 element, an element bearing one or more G4 motifs at the 5′-end of the first intron, on the non-template DNA strand. These results suggest potential roles for dynamic G4 DNA and G4 RNA structures in cis-regulation of pausing, and thus genome-wide regulation of gene expression, in human cells

    The Polyamine Inhibitor Alpha-Difluoromethylornithine Modulates Hippocampus-Dependent Function after Single and Combined Injuries

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    Exposure to uncontrolled irradiation in a radiologic terrorism scenario, a natural disaster or a nuclear battlefield, will likely be concomitantly superimposed on other types of injury, such as trauma. In the central nervous system, radiation combined injury (RCI) involving irradiation and traumatic brain injury may have a multifaceted character. This may entail cellular and molecular changes that are associated with cognitive performance, including changes in neurogenesis and the expression of the plasticity-related immediate early gene Arc. Because traumatic stimuli initiate a characteristic early increase in polyamine metabolism, we hypothesized that treatment with the polyamine inhibitor alpha-difluoromethylornithine (DFMO) would reduce the adverse effects of single or combined injury on hippocampus structure and function. Hippocampal dependent cognitive impairments were quantified with the Morris water maze and showed that DFMO effectively reversed cognitive impairments after all injuries, particularly traumatic brain injury. Similar results were seen with respect to the expression of Arc protein, but not neurogenesis. Given that polyamines have been found to modulate inflammatory responses in the brain we also assessed the numbers of total and newly born activated microglia, and found reduced numbers of newly born cells. While the mechanisms responsible for the improvement in cognition after DFMO treatment are not yet clear, the present study provides new and compelling data regarding the potential use of DFMO as a potential countermeasure against the adverse effects of single or combined injury

    Outcomes of Allogeneic Hematopoietic Cell Transplantation in Children and Young Adults with Chronic Myeloid Leukemia: A CIBMTR Cohort Analysis

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    Chronic myeloid leukemia (CML) in children and young adults is uncommon. Young patients have long life expectancies and low morbidity with hematopoietic cell transplantation (HCT). Prolonged tyrosine kinase inhibitor (TKI) use may cause significant morbidity. In addition indication for HCT in patients in first chronic phase is not established

    Interpretative and predictive modelling of Joint European Torus collisionality scans

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    Transport modelling of Joint European Torus (JET) dimensionless collisionality scaling experiments in various operational scenarios is presented. Interpretative simulations at a fixed radial position are combined with predictive JETTO simulations of temperatures and densities, using the TGLF transport model. The model includes electromagnetic effects and collisions as well as □(→┬E ) X □(→┬B ) shear in Miller geometry. Focus is on particle transport and the role of the neutral beam injection (NBI) particle source for the density peaking. The experimental 3-point collisionality scans include L-mode, and H-mode (D and H and higher beta D plasma) plasmas in a total of 12 discharges. Experimental results presented in (Tala et al 2017 44th EPS Conf.) indicate that for the H-mode scans, the NBI particle source plays an important role for the density peaking, whereas for the L-mode scan, the influence of the particle source is small. In general, both the interpretative and predictive transport simulations support the experimental conclusions on the role of the NBI particle source for the 12 JET discharges

    Helping Students With ASD Adapt to the Mainstream

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    SWOT-AHP as an inclusive analytical tool of the forest-wood-energy chain: the case study of the Sarntal (South Tyrol)

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    In the last years, the use of forest biomass for energy purpose is steadily increasing to tackle energy security issues and to mitigate climate change by stabilizing greenhouse gases (GHG) concentrations in the atmosphere. In Italy, the new National Energy Strategy established that the renewable energy must cover 20% of gross energy demand by 2020. In order to achieve this objective the forest biomass could be of fundamental importance. In this context of increasing extraction of wood residues from forests, it is relevant to analyse two key aspects: (1) the involvement of stakeholders in the strategy for the valorization of forest-wood-energy chain at local level; and (2) the potential impacts of increased forest biomass extraction on environment. This paper analyses these two aspects through the stakeholders’ opinions in a case study in the Alto Adige (Sarentino valley). Stakeholders’ opinions concerning the analysis of SWOT categories (strengths, weaknesses, opportunities, threats) of the bioenergy supply chain were investigated using the SWOT-AHP (Analytical Hierarchy Process) approach. The results show that the local stakeholders emphasize some strengths (e.g., additional income over time for private forest owners) and opportunities (e.g., development of shared forest management strategies among small forest owners) of forest-wood-energy chain, and consider less relevant the weaknesses and threats. The results concerning one of most important potential threats - impacts on environment - show that all groups of stakeholders (public administrations, associations and NGO, research bodies and universities, and actors of rural sector) consider positive the impacts of increased forest biomass extraction on recreational activities and negative on other three ecosystem services (carbon sequestration, hydrogeological protection, and biodiversity)

    Fetal meningeal hemangiopericytoma - Case report

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    The authors present the case of a 34-week-old fetus with a meningeal hemangiopericytoma that was diagnosed in utero by using abdominal magnetic resonance imaging. After birth, the neonate underwent transfontanelle ultrasonography and computerized tomography scanning of the head, which confirmed the presence of an extradural hyperdense lesion. Six hours after birth the neonate underwent a craniotomy, which resulted in complete resection of the mass. the postoperative period was uneventful and the newborn was discharged 7 days later. At 2-year follow-up examination there was no evidence of recurrence of the lesion. the authors have found no mention in the literature of this entity diagnosed in the prenatal period.Universidade Federal de São Paulo, Dept Neurosurg, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Neurosurg, São Paulo, BrazilWeb of Scienc
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