489 research outputs found

    DNA origami-based single-molecule force spectroscopy elucidates RNA Polymerase III pre-initiation complex stability

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    The TATA-binding protein (TBP) and a transcription factor (TF) IIB-like factor are important constituents of all eukaryotic initiation complexes. The reason for the emergence and strict requirement of the additional initiation factor Bdp1 in the RNA polymerase (RNAP) III system, however, remained elusive. A poorly studied aspect in this context is the effect of DNA strain arising from DNA compaction and transcriptional activity on initiation complex formation. We made use of a DNA origami-based force clamp to follow the assembly of human initiation complexes in the RNAP II and RNAP III systems at the single-molecule level under piconewton forces. We demonstrate that TBP-DNA complexes are force-sensitive and TFIIB is sufficient to stabilise TBP on a strained promoter. In contrast, Bdp1 is the pivotal component that ensures stable anchoring of initiation factors, and thus the polymerase itself, in the RNAP III system. Thereby, we offer an explanation for the crucial role of Bdp1 for the high transcriptional output of RNAP II

    Climate and land-use change during the late Holocene at Lake Ledro (southern Alps, Italy)

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    International audienceThis paper investigates the relative influences of climatic and anthropogenic factors in explaining environmental and societal changes in the southern Alps, Italy. We investigate a deep sediment core (LL081) from Lake Ledro (652 m a.s.l.). Environmental changes are reconstructed through multiproxy analysis, that is, pollen-based vegetation and climate reconstruction, magnetic susceptibility (MS), lake level, and flood frequency, and the paper focuses on the climate and land-use changes which occurred during the late Holocene. For this time interval, Lake Ledro records high mean water table, increasing amount of pollen-based precipitation, and more erosive conditions. Therefore, while a more humid late Holocene in the southern Alps has the potential to reinforce the forest presence, pollen evidence suggests that anthropogenic activities changed the impact of this regional scenario. Land-use activity (forest clearance for pastoralism, farming, and arboriculture) opened up the large vegetated slopes in the catchment of Lake Ledro, which in turn magnified the erosion related to the change in the precipitation pattern. The record of an almost continuous human occupation for the last 4100 cal. BP is divided into several land-use phases. On the one hand, forest redevelopments on abandoned or less cultivated areas appear to be climatically induced as they occurred in relation with well-known events such as the 2.8-kyr cold event and the ‘Little Ice Age’. On the other hand, climatically independent changes in land use or habitat modes are observed, such as the late-Bronze-Age lake-dwellings abandonment, the human population migration at c. 1600 cal. BP, and the period of the Black Death and famines at 600 cal. BP

    Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque

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    Carotid intima media thickness (cIMT) and plaque determined by ultrasonography are established measures of subclinical atherosclerosis that each predicts future cardiovascular disease events. We conducted a meta-analysis of genome-wide association data in 31,211 participants of European ancestry from nine large studies in the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. We then sought additional evidence to support our findings among 11,273 individuals using data from seven additional studies. In the combined meta-analysis, we identified three genomic regions associated with common carotid intima media thickness and two different regions associated with the presence of carotid plaque (P < 5 × 10 -8). The associated SNPs mapped in or near genes related to cellular signaling, lipid metabolism and blood pressure homeostasis, and two of the regions were associated with coronary artery disease (P < 0.006) in the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis (CARDIoGRAM) consortium. Our findings may provide new insight into pathways leading to subclinical atherosclerosis and subsequent cardiovascular events

    The influence of different concentrations of flavanol chocolate bars under acute supplement conditions on exercise and performance

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    The purpose of this study was to assess the effects and acute dosage of different flavanol concentrations in a dark chocolate bar on physiological parameters during steady state (SS) and incremental exercise. In a double-blind, randomised, crossover study, 15 healthy participants with a mean ± SD age of 30 ± 7 years; stature 176.8 ± 8.6 cm and body mass 80.3 ± 8.4 kg supplemented with high flavanol (HF) (1060 mg), moderate flavanol (MF) (746 mg), low flavanol (LF) (406 mg), or a control (CON) (88 mg) chocolate bar (~ 34 g), 2 h prior to 40 min of SS cycling (80% gas-exchange threshold) followed by an incremental test to volitional fatigue. During the SS cycle oxygen consumption ([Formula: see text]), respiratory exchange ratio (RER) and heart rate (HR) were continuously monitored. Plasma samples were collected prior to commencing exercise to determine nitrate (NO ) and nitrite (NO ) levels under each condition. There was no observed effect between flavanol concentrations on [Formula: see text], RER, and HR during SS cycling (P > 0.05). [Formula: see text], peak power, HR peak, and RER peak also did not significantly differ between conditions (P > 0.05). There was a small trend for higher plasma NO levels following higher flavanol concentration; however, this did not reach statistical significance (P > 0.05). Acute supplementation with cocoa of differing flavanol concentrations does not appear to have any effect on exercise and performance. It is plausible that longer flavanol supplementation periods might have greater accumulative effects and thus may potentially elicit a larger effect

    Circulating CD133+VEGFR2+ and CD34+VEGFR2+ cells and arterial function in patients with beta-thalassaemia major

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    Arterial dysfunction has been documented in patients with beta-thalassaemia major. This study aimed to determine the quantity and proliferative capacity of circulating CD133+VEGFR2+ and CD34+VEGFR2+ cells in patients with beta-thalassaemia major and those after haematopoietic stem cell transplantation (HSCT), and their relationships with arterial function. Brachial arterial flow-mediated dilation (FMD), carotid arterial stiffness, the quantity of these circulating cells and their number of colony-forming units (CFUs) were determined in 17 transfusion-dependent thalassaemia patients, 14 patients after HSCT and 11 controls. Compared with controls, both patient groups had significantly lower FMD and greater arterial stiffness. Despite having increased CD133+VEGFR2+ and CD34+VEGFR2+ cells, transfusion-dependent patients had significantly reduced CFUs compared with controls (p = 0.002). There was a trend of increasing CFUs across the three groups with decreasing iron load (p = 0.011). The CFUs correlated with brachial FMD (p = 0.029) and arterial stiffness (p = 0.02), but not with serum ferritin level. Multiple linear regression showed that CFU was a significant determinant of FMD (p = 0.043) and arterial stiffness (p = 0.02) after adjustment of age, sex, body mass index, blood pressure and serum ferritin level. In conclusion, arterial dysfunction found in patients with beta-thalassaemia major before and after HSCT may be related to impaired proliferation of CD133+VEGFR2+ and CD34+VEGFR2+ cells

    Search for New Particles Decaying to top-antitop in proton-antiproton collisions at squareroot(s)=1.8 TeV

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    We use 106 \ipb of data collected with the Collider Detector at Fermilab to search for narrow-width, vector particles decaying to a top and an anti-top quark. Model independent upper limits on the cross section for narrow, vector resonances decaying to \ttbar are presented. At the 95% confidence level, we exclude the existence of a leptophobic \zpr boson in a model of topcolor-assisted technicolor with mass M_{\zpr} << 480 \gev for natural width Γ\Gamma = 0.012 M_{\zpr}, and M_{\zpr} << 780 \gev for Γ\Gamma = 0.04 M_{\zpr}.Comment: The CDF Collaboration, submitted to PRL 25-Feb-200

    A Measurement of the Differential Dijet Mass Cross Section in p-pbar Collisions at sqrt{s}=1.8 TeV

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    We present a measurement of the cross section for production of two or more jets as a function of dijet mass, based on an integrated luminosity of 86 pb^-1 collected with the Collider Detector at Fermilab. Our dijet mass spectrum is described within errors by next-to-leading order QCD predictions using CTEQ4HJ parton distributions, and is in good agreement with a similar measurement from the D0 experiment.Comment: 18 pages including 2 figures and 3 tables. Submitted to Phys. Rev. D Rapid Communication

    A Study of B0 -> J/psi K(*)0 pi+ pi- Decays with the Collider Detector at Fermilab

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    We report a study of the decays B0 -> J/psi K(*)0 pi+ pi-, which involve the creation of a u u-bar or d d-bar quark pair in addition to a b-bar -> c-bar(c s-bar) decay. The data sample consists of 110 1/pb of p p-bar collisions at sqrt{s} = 1.8 TeV collected by the CDF detector at the Fermilab Tevatron collider during 1992-1995. We measure the branching ratios to be BR(B0 -> J/psi K*0 pi+ pi-) = (8.0 +- 2.2 +- 1.5) * 10^{-4} and BR(B0 -> J/psi K0 pi+ pi-) = (1.1 +- 0.4 +- 0.2) * 10^{-3}. Contributions to these decays are seen from psi(2S) K(*)0, J/psi K0 rho0, J/psi K*+ pi-, and J/psi K1(1270)
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