2,478 research outputs found

    Reduced expression of mir15a in the blood of patients with oral squamous cell carcinoma is associated with tumor staging

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    MicroRNAs (miRNAs) mirl 5a and let7a are iMportant regulators of bcl-2, ras and c-myc proteins Considering that these miRNAs are commonly altered in many human cancers and that these proteins are reported to be altered in oral squamous cell carcinoma (OSCC), we investigated them in a set of OSCC cases \u27I he miRNAs as well as the proteins were evaluated in the tumor and blood of 20 patients by real-time quantitative PCR and iMmunohistochemistry, respectively The expression of nfirl5a and bcl-2 proteins in the tumors was not associated with each other or with tumor staging On the other hand, we found reduced expression of this miRNA in the blood of patients with an advanced stage of OSCC and with lymph node metastasis The expression of let7a in the tumor and blood was not associated with tumor size lymph node metastasis, tumor staging and immunoexpression of ras and c-myc proteins In conclusion, the present study shows that reduced expression of Mir15a is associated with OSCC stagin

    DNA methylation alterations in grade II- and anaplastic pleomorphic xanthoastrocytoma

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    BACKGROUND: Pleomorphic xanthoastrocytoma (PXA) is a rare WHO grade II tumor accounting for less than 1% of all astrocytomas. Malignant transformation into PXA with anaplastic features, is unusual and correlates with poorer outcome of the patients. METHODS: Using a DNA methylation custom array, we have quantified the DNA methylation level on the promoter sequence of 807 cancer-related genes of WHO grade II (n = 11) and III PXA (n = 2) and compared to normal brain tissue (n = 10) and glioblastoma (n = 87) samples. DNA methylation levels were further confirmed on independent samples by pyrosequencing of the promoter sequences. RESULTS: Increasing DNA promoter hypermethylation events were observed in anaplastic PXA as compared with grade II samples. We further validated differential hypermethylation of CD81, HCK, HOXA5, ASCL2 and TES on anaplastic PXA and grade II tumors. Moreover, these epigenetic alterations overlap those described in glioblastoma patients, suggesting common mechanisms of tumorigenesis. CONCLUSIONS: Even taking into consideration the small size of our patient populations, our data strongly suggest that epigenome-wide profiling of PXA is a valuable tool to identify methylated genes, which may play a role in the malignant progression of PXA. These methylation alterations may provide useful biomarkers for decision-making in those patients with low-grade PXA displaying a high risk of malignant transformation

    Subcellular heterogeneity of ryanodine receptor properties in ventricular myocytes with low T-tubule density

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    Rationale: In ventricular myocytes of large mammals, not all ryanodine receptor (RyR) clusters are associated with T-tubules (TTs); this fraction increases with cellular remodeling after myocardial infarction (MI). Objective: To characterize RyR functional properties in relation to TT proximity, at baseline and after MI. Methods: Myocytes were isolated from left ventricle of healthy pigs (CTRL) or from the area adjacent to a myocardial infarction (MI). Ca2+ transients were measured under whole-cell voltage clamp during confocal linescan imaging (fluo-3) and segmented according to proximity of TTs (sites of early Ca2+ release, F>F50 within 20 ms) or their absence (delayed areas). Spontaneous Ca2+ release events during diastole, Ca2+ sparks, reflecting RyR activity and properties, were subsequently assigned to either category. Results: In CTRL, spark frequency was higher in proximity of TTs, but spark duration was significantly shorter. Block of Na+/Ca2+ exchanger (NCX) prolonged spark duration selectively near TTs, while block of Ca2+ influx via Ca2+ channels did not affect sparks properties. In MI, total spark mass was increased in line with higher SR Ca2+ content. Extremely long sparks (>47.6 ms) occurred more frequently. The fraction of near-TT sparks was reduced; frequency increased mainly in delayed sites. Increased duration was seen in near-TT sparks only; Ca2+ removal by NCX at the membrane was significantly lower in MI. Conclusion: TT proximity modulates RyR cluster properties resulting in intracellular heterogeneity of diastolic spark activity. Remodeling in the area adjacent to MI differentially affects these RyR subpopulations. Reduction of the number of sparks near TTs and reduced local NCX removal limit cellular Ca2+ loss and raise SR Ca2+ content, but may promote Ca2+ waves

    The young open cluster NGC 7067 using Stromgren photometry

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    © The Authors 2016. Published by Oxford University Press on behalf of The Royal Astronomical Society. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. M. Monguio et al, ' The young open cluster NGC 7067 using Stromgren photometry ', MNRAS Vol 466(3): 3636-3647 (2017), first published online 17 December 2016, the version of record is available online via doi: 10.1093/mnras/stw3302NGC 7067 is a young open cluster located in the direction between the first and the second Galactic quadrants and close to the Perseus spiral arm. This makes it useful for studies of the nature of the Milky Way spiral arms. Stromgren photometry taken with the Wide Field Camera at the Isaac Newton Telescope allowed us to compute individual physical parameters for the bserved stars and hence to derive cluster’s physical parameters. Spectra from the 1.93-m telescope at the Observatoire de Haute-Provence helped to check and improve the results. We obtained photometry for 1233 stars, individual physical parameters for 515 and spectra for 9 of them. The 139 selected cluster members lead to a cluster distance of 4.4±0.4 kpc, with an age below log10(t(yr))=7.3 and a present Mass of 1260±160M⊙. The morphology of the data reveals that the centre of the cluster is at (α,δ)=(21: 24: 13.69,+48: 00: 39.2) J2000, with a radius of 6.′1. Stromgren and spectroscopic data allowed us to improve the previous parameters available for the cluster in the literature.Peer reviewedFinal Published versio

    Constraining the string scale: from Planck to Weak and back again

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    String and field theory ideas have greatly influenced each other since the so called second string revolution. We review this interrelation paying particular attention to its phenomenological implications. Our guiding principle is the radical shift in the way that we think about the fundamental scale, in particular the way in which string models have been able to accommodate values from the Planck MPl1018M_\mathrm{Pl}\sim 10^{18} GeV down to the electroweak scale MEWM_{EW}\sim TeV.Comment: Invited review aimed at an experimental audienc

    The Determination of alpha_s from Tau Decays Revisited

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    We revisit the determination of alpha_s(m_tau) using a fit to inclusive tau hadronic spectral moments in light of (1) the recent calculation of the fourth-order perturbative coefficient K_4 in the expansion of the Adler function, (2) new precision measurements from BABAR of e+e- annihilation cross sections, which decrease the uncertainty in the separation of vector and axial-vector spectral functions, and (3) improved results from BABAR and Belle on tau branching fractions involving kaons. We estimate that the fourth-order perturbative prediction reduces the theoretical uncertainty, introduced by the truncation of the series, by 20% with respect to earlier determinations. We discuss to some detail the perturbative prediction and show that the effect of the incomplete knowledge of the series is reduced by using the so-called contour-improved calculation, as opposed to fixed-order perturbation theory which manifests convergence problems. The corresponding theoretical uncertainties are studied at the tau and Z mass scales. Nonperturbative contributions extracted from the most inclusive fit are small, in agreement with earlier determinations. Systematic effects from quark-hadron duality violation are estimated with simple models and found to be within the quoted systematic errors. The fit gives alpha_s(m_tau) = 0.344 +- 0.005 +- 0.007, where the first error is experimental and the second theoretical. After evolution to M_Z we obtain alpha_s(M_Z) = 0.1212 +- 0.0005 +- 0.0008 +- 0.0005, where the errors are respectively experimental, theoretical and due to the evolution. The result is in agreement with the corresponding NNNLO value derived from essentially the Z width in the global electroweak fit. The alpha_s(M_Z) determination from tau decays is the most precise one to date.Comment: 22 pages, 7 figure

    Intersecting Brane Worlds -- A Path to the Standard Model ?

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    In this review we describe the general geometrical framework of brane world constructions in orientifolds of type IIA string theory with D6-branes wrapping 3-cycles in a Calabi-Yau 3-fold. These branes generically intersect in points on the internal space, and the patterns of intersections govern the chiral fermion spectra. We discuss how the open string spectra in intersecting brane models are constructed, how the Standard Model can be embedded, and also how supersymmetry can be realized in this class of string vacua. After the general considerations we specialize the discussion to the case of orbifold backgrounds with intersecting D6-branes and to the quintic Calabi-Yau manifold. Then, we discuss parts of the effective action of intersecting brane world models. Specifically we compute from the Born-Infeld action of the wrapped D-branes the tree-level, D-term scalar potential, which is important for the stability of the considered backgrounds as well as for questions related to supersymmetry breaking. Second, we review the recent computation concerning of gauge coupling unification and also of one-loop gauge threshold corrections in intersecting brane world models. Finally we also discuss some aspects of proton decay in intersecting brane world models.Comment: 31 pages, To appear in the proceedings of the RTN-workshop ``The quantum structure of spacetime and the geometric nature of fundamental interactions'', September 2003 in Copenhagen, revised version contains new refs and one corrected equatio
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