461 research outputs found
Cellular senescence impairs the reversibility of pulmonary arterial hypertension
Pulmonary arterial hypertension (PAH) in congenital cardiac shunts can be reversed by hemodynamic unloading (HU) through shunt closure. However, this reversibility potential is lost beyond a certain point in time. The reason why PAH becomes irreversible is unknown. In this study, we used MCT+shunt-induced PAH in rats to identify a dichotomous reversibility response to HU, similar to the human situation. We compared vascular profiles of reversible and irreversible PAH using RNA sequencing. Cumulatively, we report that loss of reversibility is associated with a switch from a proliferative to a senescent vascular phenotype and confirmed markers of senescence in human PAH-CHD tissue. In vitro, we showed that human pulmonary endothelial cells of patients with PAH are more vulnerable to senescence than controls in response to shear stress and confirmed that the senolytic ABT263 induces apoptosis in senescent, but not in normal, endothelial cells. To support the concept that vascular cell senescence is causal to the irreversible nature of end-stage PAH, we targeted senescence using ABT263 and induced reversal of the hemodynamic and structural changes associated with severe PAH refractory to HU. The factors that drive the transition from a reversible to irreversible pulmonary vascular phenotype could also explain the irreversible nature of other PAH etiologies and provide new leads for pharmacological reversal of end-stage PAH
Hot Subdwarfs from the Stable Roche Lobe Overflow Channel
In this study, we concentrate on the formation and evolution of hot subdwarfs
binaries through the stable Roche lobe overflow (RLOF) channel of
intermediate-mass binaries. We aim at setting out the properties of hot
subdwarfs and their progenitors, so that we can understand the formation and
evolution of hot subdwarfs comprehensively. We have obtained the ranges of the
initial parameters of progenitor binaries and the properties of hot subdwarfs
through the stable RLOF channel of intermediate-mass binaries, e.g. mass,
envelope mass and age of hot subdwarfs. We have found that hot subdwarfs could
be formed through the stable Roche lobe overflow at main sequence and
Hertzsprung gap. We have also found that some subdwarf B or OB stars have
anomalous high mass (around 1 solar mass) with thick envelope (0.07 solar mass
to 0.16 solar mass) in our models. By comparing our theoretical results with
observations on the hot subdwarfs in open clusters, we suppose a quantity of
hot subdwarfs in binary systems might be found in open clusters in the future.Comment: 13 pages, 15 figures, published in Astronomy and Astrophysic
Species by Environment Interactions Affect Pyrrolizidine Alkaloid Expression in Senecio jacobaea, Senecio aquaticus, and Their Hybrids
We examined the effects of water and nutrient availability on the expression of the defense pyrrolizidine alkaloids (PAs) in Senecio jacobaea and S. aquaticus. Senecio jacobaea, and S. aquaticus are adapted to different natural habitats, characterized by differing abiotic conditions and different selection pressures from natural enemies. We tested if PA concentration and diversity are plastic over a range of water and nutrient treatments, and also whether such plasticity is dependent on plant species. We also tested the hypothesis that hybridization may contribute to PA diversity within plants, by comparing PA expression in parental species to that in artificially generated F1 hybrids, and also in later generation natural hybrids between S. jacobaea and S. aquaticus. We showed that total PA concentration in roots and shoots is not dependent on species, but that species determines the pattern of PA diversification. Pyrrolizidine alkaloid diversity and concentration are both dependent on environmental factors. Hybrids produce a putatively novel PA, and this PA is conserved in natural hybrids, that are backcrossed to S. jacobaea. Natural hybrids that are backcrossed several times to S. jacobaea are with regard to PA diversity significantly different from S. jacobaea but not from S. aquaticus, while F1 hybrids are in all cases more similar to S. jacobaea. These results collectively suggest that PA diversity is under the influence of natural selection
Patients lacking classical poor prognostic markers might also benefit from a step-down glucocorticoid bridging scheme in early rheumatoid arthritis: week 16 results from the randomized multicenter CareRA trial
Measurement of the prompt J/psi and psi(2S) polarizations in pp collisions at sqrt(s) = 7 TeV
The polarizations of prompt J/psi and psi(2S) mesons are measured in proton-proton collisions at sqrt(s) = 7 TeV, using a dimuon data sample collected by the CMS experiment at the LHC, corresponding to an integrated luminosity of 4.9 inverse femtobarns. The prompt J/psi and psi(2S) polarization parameters lambda[theta], lambda[phi], and lambda[theta, phi], as well as the frame-invariant quantity lambda(tilde), are measured from the dimuon decay angular distributions in three different polarization frames. The J/psi results are obtained in the transverse momentum range 14 < pt < 70 GeV, in the rapidity intervals abs(y) < 0.6 and 0.6 < abs(y) < 1.2. The corresponding psi(2S) results cover 14 < pt < 50 GeV and include a third rapidity bin, 1.2 < abs(y) < 1.5. No evidence of large transverse or longitudinal polarizations is seen in these kinematic regions, which extend much beyond those previously explored
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