Profiling Three-Dimensional Nuclear Telomeric Architecture of Myelodysplastic Syndromes and Acute Myeloid Leukemia Defines Patient Subgroups

Purpose: Myelodysplastic syndromes (MDS) are a group of disorders characterized by cytopenias, with a propensity for evolution into acute myeloid leukemias (AML). This transformation is driven by genomic instability, but mechanisms remain unknown. Telomere dysfunction might generate genomic instability leading to cytopenias and disease progression. Experimental Design: We undertook a pilot study of 94 patients with MDS (56 patients) and AML (38 patients). The MDS cohort consisted of refractory cytopenia with multilineage dysplasia (32 cases), refractory anemia (12 cases), refractory anemia with excess of blasts (RAEB) 1 (8 cases), RAEB2 (1 case), refractory anemia with ring sideroblasts (2 cases), and MDS with isolated del(5q) (1 case). The AML cohort was composed of AML-M4 (12 cases), AML-M2 (10 cases), AML-M5 (5 cases), AML-M0 (5 cases), AML-M1 (2 cases), AML-M4eo (1 case), and AML with multidysplasia-related changes (1 case). Three-dimensional quantitative FISH of telomeres was carried out on nuclei from bone marrow samples and analyzed using TeloView. Results: We defined three-dimensional nuclear telomeric profiles on the basis of telomere numbers, telomeric aggregates, telomere signal intensities, nuclear volumes, and nuclear telomere distribution. Using these parameters, we blindly subdivided the MDS patients into nine subgroups and the AML patients into six subgroups. Each of the parameters showed significant differences between MDS and AML. Combining all parameters revealed significant differences between all subgroups. Three-dimensional telomeric profiles are linked to the evolution of telomere dysfunction, defining a model of progression from MDS to AML. Conclusions: Our results show distinct three-dimensional telomeric profiles specific to patients with MDS and AML that help subgroup patients based on the severity of telomere dysfunction highlighted in the profiles. Clin Cancer Res; 18(12); 3293-304. (C) 2012 AACR.

Tomotherapy dose distribution verification using MAGIC-f polymer gel dosimetry

Purpose: This paper presents the application of MAGIC-f gel in a three-dimensional dose distribution measurement and its ability to accurately measure the dose distribution from a tomotherapy unit. Methods: A prostate intensity-modulated radiation therapy (IMRT) irradiation was simulated in the gel phantom and the treatment was delivered by a TomoTherapy equipment. Dose distribution was evaluated by the R2 distribution measured in magnetic resonance imaging. Results: A high similarity was found by overlapping of isodoses of the dose distribution measured with the gel and expected by the treatment planning system (TPS). Another analysis was done by comparing the relative absorbed dose profiles in the measured and in the expected dose distributions extracted along indicated lines of the volume and the results were also in agreement. The gamma index analysis was also applied to the data and a high pass rate was achieved (88.4% for analysis using 3%/3 mm and of 96.5% using 4%/4 mm). The real three-dimensional analysis compared the dose-volume histograms measured for the planning volumes and expected by the treatment planning, being the results also in good agreement by the overlapping of the curves. Conclusions: These results show that MAGIC-f gel is a promise for tridimensional dose distribution measurements. (C) 2012 American Association of Physicists in Medicine. [http://dx.doi.org/10.1118/1.4704496]

Nuclear-modification factor for open-heavy-flavor production at forward rapidity in Cu plus Cu collisions at root s(NN)=200 GeV

Background: Heavy-flavor production in p + p collisions is a good test of perturbative-quantum-chromodynamics (pQCD) calculations. Modification of heavy-flavor production in heavy-ion collisions relative to binary-collision scaling from p + p results, quantified with the nuclear-modification factor (R-AA), provides information on both cold-and hot-nuclear-matter effects. Midrapidity heavy-flavor R-AA measurements at the Relativistic Heavy Ion Collider have challenged parton-energy-loss models and resulted in upper limits on the viscosity-entropy ratio that are near the quantum lower bound. Such measurements have not been made in the forward-rapidity region. Purpose: Determine transverse-momentum (p(T)) spectra and the corresponding R-AA for muons from heavy-flavor meson decay in p + p and Cu + Cu collisions at root s(NN) = 200 GeV and y = 1.65. Method: Results are obtained using the semileptonic decay of heavy-flavor mesons into negative muons. The PHENIX muon-arm spectrometers measure the p(T) spectra of inclusive muon candidates. Backgrounds, primarily due to light hadrons, are determined with a Monte Carlo calculation using a set of input hadron distributions tuned to match measured-hadron distributions in the same detector and statistically subtracted. Results: The charm-production cross section in p + p collisions at root s = 200 GeV, integrated over p(T) and in the rapidity range 1.4 < y < 1.9, is found to be d(sigma e (e) over bar)/dy = 0.139 +/- 0.029 (stat)(-0.058)(+0.051) (syst) mb. This result is consistent with a perturbative fixed-order-plus-next-to-leading-log calculation within scale uncertainties and is also consistent with expectations based on the corresponding midrapidity charm-production cross section measured by PHENIX. The R-AA for heavy-flavor muons in Cu + Cu collisions is measured in three centrality bins for 1 < p(T) < 4 GeV/c. Suppression relative to binary-collision scaling (R-AA < 1) increases with centrality. Conclusions: Within experimental and theoretical uncertainties, the measured charm yield in p + p collisions is consistent with state-of-the-art pQCD calculations. Suppression in central Cu + Cu collisions suggests the presence of significant cold-nuclear-matter effects and final-state energy loss.

Cation Distribution and Local Order in Mixed Sodium Metaphosphate Glasses

Two structural properties in mixed alkali metal phosphate glasses that seem to be crucial to the development of the mixed ion effect in dc conductivity were systematically analyzed in Na mixed metaphosphates: the local order around the mobile species, and their distribution and mixing in the glass network. The set of glasses considered here, Na1-xMxPO3 with M = Li, Ag, K, Rb, and Cs and 0 <= x <= 1, encompass a broad degree of size mismatch between the mixed cation species. A comprehensive solid-state nuclear magnetic resonance study was carried out using P-31 MAS, Na-23 triple quantum MAS, Rb-87 QCPMG, P-31-Na-23 REDOR, Na-23-Li-7 and Li-7-Li-6 SEDOR, and Na-23 spin echo decay. It was observed that the arrangement of P atoms around Na in the mixed glasses was indistinguishable from that observed in the NaPO3 glass. However, systematic distortions in the local structure of the 0 environments around Na were observed, related to the presence of the second cation. The average Na-O distances show an expansion/compression When Na+ ions are replaced by cations with respectively smaller/bigger radii. The behavior of the nuclear electric quadrupole coupling. constants indicates that this expansion reduces the local symmetry, while the compression produces the opposite effect These effects become marginally small when the site mismatch between the cations is small, as in Na-Ag mixed glasses. The present study confirms the intimate mixing of cation species at the atomic scale, but clear deviations from random mixing were detected in systems with larger alkali metal ions (Cs-Na, K-Na, Rb-Na). In contrast, no deviations from the statistical ion mixture were found in the systems Ag-Na and Li-Na, where mixed cations are either of radii comparable to (Ag+) or smaller than (Li+) Na+. The set of results supports two fundamental structural features of the models proposed to explain the mixed ion effect: the. structural specificity of the sites occupied by each cation species and their mixing at the atomic scale.

Genetic variability in mitochondrial and nuclear genes of Larus dominicanus (Charadriiformes, Laridae) from the Brazilian coast

Several phylogeographic studies of seabirds have documented low genetic diversity that has been attributed to bottleneck events or individual capacity for dispersal. Few studies have been done in seabirds on the Brazilian coast and all have shown low genetic differentiation on a wide geographic scale. The Kelp Gull is a common species with a wide distribution in the Southern Hemisphere. In this study, we used mitochondrial and nuclear markers to examine the genetic variability of Kelp Gull populations on the Brazilian coast and compared this variability with that of sub-Antarctic island populations of this species. Kelp Gulls showed extremely low genetic variability for nnitochondrial markers (cytb and ATPase) and high diversity for a nuclear locus (intron 7 of the beta-fibrinogen). The intraspecific evolutionary history of Kelp Gulls showed that the variability found in intron 7 of the beta-fibrinogen gene was compatible with the variability expected under neutral evolution but suggested an increase in population size during the last 10,000 years. However, none of the markers revealed evidence of a bottleneck population. These findings indicate that the recent origin of Kelp Gulls is the main explanation for their nuclear diversity, although selective pressure on the mtDNA of this species cannot be discarded.

Measurement of Direct Photons in Au plus Au Collisions at root s(NN)=200 GeV

We report the measurement of direct photons at midrapidity in Au + Au collisions at root s(NN) = 200 GeV. The direct photon signal was extracted for the transverse momentum range of 4 GeV/c < pT < 22 GeV/c, using a statistical method to subtract decay photons from the inclusive photon sample. The direct photon nuclear modification factor R-AA was calculated as a function of p(T) for different Au + Au collision centralities using the measured p + p direct photon spectrum and compared to theoretical predictions. R-AA was found to be consistent with unity for all centralities over the entire measured pT range. Theoretical models that account for modifications of initial direct photon production due to modified parton distribution functions in Au and the different isospin composition of the nuclei predict a modest change of R-AA from unity. They are consistent with the data. Models with compensating effects of the quark-gluon plasma on high-energy photons, such as suppression of jet-fragmentation photons and induced-photon bremsstrahlung from partons traversing the medium, are also consistent with this measurement.

On the radial expansion of tubular structures in a quark-gluon plasma

We study the radial expansion of cylindrical tubes in a hot QGP. These tubes are treated as perturbations in the energy density of the system which is formed in heavy ion collisions at RHIC and LHC. We start from the equations of relativistic hydrodynamics in two spatial dimensions and cylindrical symmetry and perform an expansion of these equations in a small parameter, conserving the nonlinearity of the hydrodynamical formalism. We consider both ideal and viscous fluids and the latter are studied with a relativistic Navier-Stokes equation. We use the equation of state of the MIT bag model. In the case of ideal fluids we obtain a breaking wave equation for the energy density fluctuation, which is then solved numerically. We also show that, under certain assumptions, perturbations in a relativistic viscous fluid are governed by the Burgers equation. We estimate the typical expansion time of the tubes. (C) 2012 Elsevier B.V. All rights reserved.

Cold-Nuclear-Matter Effects on Heavy-Quark Production in d+Au Collisions at root S-NN=200 GeV

The PHENIX experiment has measured electrons and positrons at midrapidity from the decays of hadrons containing charm and bottom quarks produced in d + Au and p + p collisions at root S-NN = 200 GeV in the transverse-momentum range 0.85 <= p(T)(e) <= 8.5 GeV/c. In central d + Au collisions, the nuclear modification factor R-dA at 1.5 < p(T) < 5 GeV/c displays evidence of enhancement of these electrons, relative to those produced in p + p collisions, and shows that the mass-dependent Cronin enhancement observed at the Relativistic Heavy Ion Collider extends to the heavy D meson family. A comparison with the neutral-pion data suggests that the difference in cold-nuclear-matter effects on light- and heavy-flavor mesons could contribute to the observed differences between the pi(0) and heavy-flavor-electron nuclear modification factors R-AA. DOI: 10.1103/PhysRevLett.109.242301

Nuclear Factor (NF) κB polymorphism is associated with heart function in patients with heart failure

Abstract Background Cardiac remodeling is generally an adverse sign and is associated with heart failure (HF) progression. NFkB, an important transcription factor involved in many cell survival pathways, has been implicated in the remodeling process, but its role in the heart is still controversial. Recently, a promoter polymorphism associated with a lesser activation of the NFKB1 gene was also associated with Dilated Cardiomyopathy. The purpose of this study was to evaluate the association of this polymorphism with clinical and functional characteristics of heart failure patients of different etiologies. Methods A total of 493 patients with HF and 916 individuals from a cohort of individuals from the general population were investigated. The NFKB1 -94 insertion/deletion ATTG polymorphism was genotyped by High Resolution Melt discrimination. Allele and genotype frequencies were compared between groups. In addition, frequencies or mean values of different phenotypes associated with cardiovascular disease were compared between genotype groups. Finally, patients were prospectively followed-up for death incidence and genotypes for the polymorphism were compared regarding disease onset and mortality incidence in HF patients. Results We did not find differences in genotype and allelic frequencies between cases and controls. Interestingly, we found an association between the ATTG1/ATTG1 genotype with right ventricle diameter (P = 0.001), left ventricle diastolic diameter (P = 0.04), and ejection fraction (EF) (P = 0.016), being the genotype ATTG1/ATTG1 more frequent in patients with EF lower than 50% (P = 0.01). Finally, we observed a significantly earlier disease onset in ATTG1/ATTG1 carriers. Conclusion There is no genotype or allelic association between the studied polymorphism and the occurrence of HF in the tested population. However, our data suggest that a diminished activation of NFKB1, previously associated with the ATTG1/ATTG1 genotype, may act modulating on the onset of disease and, once the individual has HF, the genotype may modulate disease severity by increasing cardiac remodeling and function deterioration.

Cocaine induces cell death and activates the transcription nuclear factor kappa-b in pc12 cells

Cocaine is a worldwide used drug and its abuse is associated with physical, psychiatric and social problems. The mechanism by which cocaine causes neurological damage is very complex and involves several neurotransmitter systems. For example, cocaine increases extracellular levels of dopamine and free radicals, and modulates several transcription factors. NF-κB is a transcription factor that regulates gene expression involved in cellular death. Our aim was to investigate the toxicity and modulation of NF-κB activity by cocaine in PC 12 cells. Treatment with cocaine (1 mM) for 24 hours induced DNA fragmentation, cellular membrane rupture and reduction of mitochondrial activity. A decrease in Bcl-2 protein and mRNA levels, and an increase in caspase 3 activity and cleavage were also observed. In addition, cocaine (after 6 hours treatment) activated the p50/p65 subunit of NF-κB complex and the pretreatment of the cells with SCH 23390, a D1 receptor antagonist, attenuated the NF-κB activation. Inhibition of NF-κB activity by using PDTC and Sodium Salicilate increased cell death caused by cocaine. These results suggest that cocaine induces cell death (apoptosis and necrosis) and activates NF-κB in PC12 cells. This activation occurs, at least partially, due to activation of D1 receptors and seems to have an anti-apoptotic effect on these cells.

Natural radionuclides distribution in the shelf and upper slope off southeast Brazil

In recent decades, Oceanography has been using a variety of radionuclides as tracers to understand the ocean dynamic processes, handling and disposal of sediments of seabed. In this context, the determination of natural radionuclides distributions (238U, 232Th and 40K) has been carried out with sediments samples from the shelf and upper slope off Southeast Brazil using a gamma spectrometry technique. The samples were sliced into strata of 2 cm, dried, ground and properly packed to be analysed. The concentration of activities was performed in a hyperpure Ge detector with a resolution of 1,9 keV for the peak of 1332,3 keV of 60Co, model GEM50P by EGG&ORTEC. The study area is located between latitudes 28°40'S and 23°00'S and extends from Cabo Frio (RJ) to Cabo de Santa Marta Grande (SC). The activity concentrations varied from 0,6 to 52,8 BqKg-1 for 238U, from 1,6 to 50,9BqKg-1 for 232Th and from 65,4 to 873,3 BqKg-1 for 40K. From these results it is possible to establish a correlation between the depositional area dynamics and the samples size parameters