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

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

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

Interpretative and predictive modelling of Joint European Torus collisionality scans

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

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

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

Gas-phase acylation reactions. Formation of free benzoyl cations in the gas phase

The β-decay of benzene-1,4-t2 in a large excess of CO(g) contg. EtOH or C6H6 gave 4.9% PhOEt and 95.1% PhCO2Et, and 96.9% Ph2 and 3.1% PhCO2H, resp. The results substantiate the intermediacy of PhCO+ which shows high substance discrimination forming PhOEt and PhCO2Et with EtOH, an n-type base, but no corresponding ethers or esters with C6H6, a π-type base

The origin of sea salt in snow on Arctic sea ice and in coastal regions

International audienceSnow, through its trace constituents, can have a major impact on lower tropospheric chemistry, as evidenced by ozone depletion events (ODEs) in oceanic polar areas. These ODEs are caused by the chemistry of bromine compounds, that originate from sea salt bromide. According to current ideas, bromide may be supplied to the snow surface either by upward migration from sea ice or by frost flowers being wind-blown to the snow surface. We investigate here the relative importance of both these processes by analyzing mineral ions in snow samples collected near Alert and Ny-Ålesund (Canadian and European high Arctic) in winter and spring. Vertical ionic profiles in the snowpack on sea ice are measured to test upward migration of sea salt ions and to seek evidence for ion fractionation processes. Time series of the ionic composition of surface snow layers are investigated to quantify wind-transported ions. Upward migration of unfractionated sea salt, to heights of at least 17 cm, was observed in snow sampled in winter, at temperatures near -30°C, leading to Cl- concentration of several hundred µM. Upward migration thus has the potential to supply ions to surface snow layers. Time series show that wind can deposit aerosols to the top few cm of the snow, leading also to Cl- concentrations of several hundred µM, so that both migration from sea ice and wind transport can significantly contribute ions to snow. At Ny-Ålesund, sea salt transported by wind was unfractionated, implying that it does not come from frost flowers. In the Arctic, frost flowers thus do not appear necessary to lead to large sea salt concentrations in surface snow, and to supply the bromide needed for ODEs. The data obtained also indicate that ODEs lead to significant deposition of Br- to snow. We speculate that this can also take place in coastal regions and contribute to propagate ODEs inland. Finally, we stress the need to measure snow physical parameters such as permeability and specific surface area, to understand quantitatively changes in snow chemistry

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

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)