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Raf kinases mediate the phosphorylation of eukaryotic translation elongation factor 1A and regulate its stability in eukaryotic cells
We identified eukaryotic translation elongation factor 1A (eEF1A) Raf-mediated phosphorylation sites and defined their role in the regulation of eEF1A half-life and of apoptosis of human cancer cells. Mass spectrometry identified in vitro S21 and T88 as phosphorylation sites mediated by B-Raf but not C-Raf on eEF1A1 whereas S21 was phosphorylated on eEF1A2 by both B- and C-Raf. Interestingly, S21 belongs to the first eEF1A GTP/GDP-binding consensus sequence. Phosphorylation of S21 was strongly enhanced when both eEF1A isoforms were preincubated prior the assay with C-Raf, suggesting that the eEF1A isoforms can heterodimerize thus increasing the accessibility of S21 to the phosphate. Overexpression of eEF1A1 in COS 7 cells confirmed the phosphorylation of T88 also in vivo. Compared with wt, in COS 7 cells overexpressed phosphodeficient (A) and phospho-mimicking (D) mutants of eEF1A1 (S21A/D and T88A/D) and of eEF1A2 (S21A/D), resulted less stable and more rapidly proteasome degraded. Transfection of S21 A/D eEF1A mutants in H1355 cells increased apoptosis in comparison with the wt isoforms. It indicates that the blockage of S21 interferes with or even supports C-Raf induced apoptosis rather than cell survival. Raf-mediated regulation of this site could be a crucial mechanism involved in the functional switching of eEF1A between its role in protein biosynthesis and its participation in other cellular processes
Quantum dynamics and thermalization for out-of-equilibrium phi^4-theory
The quantum time evolution of \phi^4-field theory for a spatially homogeneous
system in 2+1 space-time dimensions is investigated numerically for
out-of-equilibrium initial conditions on the basis of the Kadanoff-Baym
equations including the tadpole and sunset self-energies. Whereas the tadpole
self-energy yields a dynamical mass, the sunset self-energy is responsible for
dissipation and an equilibration of the system. In particular we address the
dynamics of the spectral (`off-shell') distributions of the excited quantum
modes and the different phases in the approach to equilibrium described by
Kubo-Martin-Schwinger relations for thermal equilibrium states. The
investigation explicitly demonstrates that the only translation invariant
solutions representing the stationary fixed points of the coupled equation of
motions are those of full thermal equilibrium. They agree with those extracted
from the time integration of the Kadanoff-Baym equations in the long time
limit. Furthermore, a detailed comparison of the full quantum dynamics to more
approximate and simple schemes like that of a standard kinetic (on-shell)
Boltzmann equation is performed. Our analysis shows that the consistent
inclusion of the dynamical spectral function has a significant impact on
relaxation phenomena. The different time scales, that are involved in the
dynamical quantum evolution towards a complete thermalized state, are discussed
in detail. We find that far off-shell 1 3 processes are responsible for
chemical equilibration, which is missed in the Boltzmann limit. Finally, we
address briefly the case of (bare) massless fields. For sufficiently large
couplings we observe the onset of Bose condensation, where our scheme
within symmetric \phi^4-theory breaks down.Comment: 77 pages, 26 figure
Formation of dense partonic matter in relativistic nucleus-nucleus collisions at RHIC: Experimental evaluation by the PHENIX collaboration
Extensive experimental data from high-energy nucleus-nucleus collisions were
recorded using the PHENIX detector at the Relativistic Heavy Ion Collider
(RHIC). The comprehensive set of measurements from the first three years of
RHIC operation includes charged particle multiplicities, transverse energy,
yield ratios and spectra of identified hadrons in a wide range of transverse
momenta (p_T), elliptic flow, two-particle correlations, non-statistical
fluctuations, and suppression of particle production at high p_T. The results
are examined with an emphasis on implications for the formation of a new state
of dense matter. We find that the state of matter created at RHIC cannot be
described in terms of ordinary color neutral hadrons.Comment: 510 authors, 127 pages text, 56 figures, 1 tables, LaTeX. Submitted
to Nuclear Physics A as a regular article; v3 has minor changes in response
to referee comments. Plain text data tables for the points plotted in figures
for this and previous PHENIX publications are (or will be) publicly available
at http://www.phenix.bnl.gov/papers.htm
Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.
BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362
Experimental study of monazite/melt partitioning with implications for the REE, Th and U geochemistry of crustal rocks
Erratum: Modelling of Impurity Transport in the Linear Plasma Devices PISCES-B and Piot-PSI Using the Monte-Carlo Code ERO
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