Absence of an embryonic stem cell DNA methylation signature in human cancer.

BackgroundDifferentiated cells that arise from stem cells in early development contain DNA methylation features that provide a memory trace of their fetal cell origin (FCO). The FCO signature was developed to estimate the proportion of cells in a mixture of cell types that are of fetal origin and are reminiscent of embryonic stem cell lineage. Here we implemented the FCO signature estimation method to compare the fraction of cells with the FCO signature in tumor tissues and their corresponding nontumor normal tissues.MethodsWe applied our FCO algorithm to discovery data sets obtained from The Cancer Genome Atlas (TCGA) and replication data sets obtained from the Gene Expression Omnibus (GEO) data repository. Wilcoxon rank sum tests, linear regression models with adjustments for potential confounders and non-parametric randomization-based tests were used to test the association of FCO proportion between tumor tissues and nontumor normal tissues. P-values of < 0.05 were considered statistically significant.ResultsAcross 20 different tumor types we observed a consistently lower FCO signature in tumor tissues compared with nontumor normal tissues, with 18 observed to have significantly lower FCO fractions in tumor tissue (total n = 6,795 tumor, n = 922 nontumor, P < 0.05). We replicated our findings in 15 tumor types using data from independent subjects in 15 publicly available data sets (total n = 740 tumor, n = 424 nontumor, P < 0.05).ConclusionsThe results suggest that cancer development itself is substantially devoid of recapitulation of normal embryologic processes. Our results emphasize the distinction between DNA methylation in normal tightly regulated stem cell driven differentiation and cancer stem cell reprogramming that involves altered methylation in the service of great cell heterogeneity and plasticity

On The Reduced Canonical Quantization Of The Induced 2D-Gravity

The quantization of the induced 2d-gravity on a compact spatial section is carried out in three different ways. In the three approaches the supermomentum constraint is solved at the classical level but they differ in the way the hamiltonian constraint is imposed. We compare these approaches establishing an isomorphism between the resulting Hilbert spaces.Comment: 17 pages, plain LaTeX. FTUV/93-15, IFIC/93-10, Imperial-TP/93-94/1

Exact Finite-Size-Scaling Corrections to the Critical Two-Dimensional Ising Model on a Torus

We analyze the finite-size corrections to the energy and specific heat of the critical two-dimensional spin-1/2 Ising model on a torus. We extend the analysis of Ferdinand and Fisher to compute the correction of order L^{-3} to the energy and the corrections of order L^{-2} and L^{-3} to the specific heat. We also obtain general results on the form of the finite-size corrections to these quantities: only integer powers of L^{-1} occur, unmodified by logarithms (except of course for the leading $\log L$ term in the specific heat); and the energy expansion contains only odd powers of L^{-1}. In the specific-heat expansion any power of L^{-1} can appear, but the coefficients of the odd powers are proportional to the corresponding coefficients of the energy expansion.Comment: 26 pages (LaTeX). Self-unpacking file containing the tex file and three macros (indent.sty, eqsection.sty, subeqnarray.sty). Added discussions on the results and new references. Version to be published in J. Phys.

Diffeomorphisms, Noether Charges and Canonical Formalism in 2D Dilaton Gravity

We carry out a parallel study of the covariant phase space and the conservation laws of local symmetries in two-dimensional dilaton gravity. Our analysis is based on the fact that the Lagrangian can be brought to a form that vanishes on-shell giving rise to a well-defined covariant potential for the symplectic current. We explicitly compute the symplectic structure and its potential and show that the requirement to be finite and independent of the Cauchy surface restricts the asymptotic symmetries.Comment: 14 pages, latex with psfig macro, one figur

Modifying the photodetachment near a metal surface by a weak electric field

We show the photodetachment cross sections of H near a metal surface can be modified using a weak static electric field. The modification is possible because the oscillatory part of the cross section near a metal surface is directly connected with the transit-time and the action of the detached-electron closed-orbit which can be changed systematically by varying the static electric field strength. Photodetachment cross sections for various photon energies and electric field values are calculated and displayed.Comment: 16 pages, 7 figure

Carbon-rich dust production in metal-poor galaxies in the Local Group

We have observed a sample of 19 carbon stars in the Sculptor, Carina, Fornax, and Leo I dwarf spheroidal galaxies with the Infrared Spectrograph on the Spitzer Space Telescope. The spectra show significant quantities of dust around the carbon stars in Sculptor, Fornax, and Leo I, but little in Carina. Previous comparisons of carbon stars with similar pulsation properties in the Galaxy and the Magellanic Clouds revealed no evidence that metallicity affected the production of dust by carbon stars. However, the more metal-poor stars in the current sample appear to be generating less dust. These data extend two known trends to lower metallicities. In more metal-poor samples, the SiC dust emission weakens, while the acetylene absorption strengthens. The bolometric magnitudes and infrared spectral properties of the carbon stars in Fornax are consistent with metallicities more similar to carbon stars in the Magellanic Clouds than in the other dwarf spheroidals in our sample. A study of the carbon budget in these stars reinforces previous considerations that the dredge-up of sufficient quantities of carbon from the stellar cores may trigger the final superwind phase, ending a star's lifetime on the asymptotic giant branch.Comment: ApJ, in press, 21 pages, 12 figures. Replaced Fig 12, corrected two reference

Free Fields for Chiral 2D Dilaton Gravity

We give an explicit canonical transformation which transforms a generic chiral 2D dilaton gravity model into a free field theory.Comment: LaTeX file, 4 pages, to appear in Phys. Rev.

Gestational hypothyroxinemia affects its offspring with a reduced suppressive capacity impairing the outcome of the experimental autoimmune encephalomyelitis

Indexación: Scopus.Hypothyroxinemia (Hpx) is a thyroid hormone deficiency (THD) condition highly frequent during pregnancy, which although asymptomatic for the mother, it can impair the cognitive function of the offspring. Previous studies have shown that maternal hypothyroidism increases the severity of experimental autoimmune encephalomyelitis (EAE), an autoimmune disease model for multiple sclerosis (MS). Here, we analyzed the immune response after EAE induction in the adult offspring gestated in Hpx. Mice gestated in Hpx showed an early appearance of EAE symptoms and the increase of all parameters of the disease such as: the pathological score, spinal cord demyelination, and immune cell infiltration in comparison to the adult offspring gestated in euthyroidism. Isolated CD4+CD25+ T cells from spleen of the offspring gestated in Hpx that suffer EAE showed reduced capacity to suppress proliferation of effector T cells (TEff) after being stimulated with anti-CD3 and anti-CD28 antibodies. Moreover, adoptive transfer experiments of CD4+CD25+ T cells from the offspring gestated in Hpx suffering EAE to mice that were induced with EAE showed that the receptor mice suffer more intense EAE pathological score. Even though, no significant differences were detected in the frequency of Treg cells and IL-10 content in the blood, spleen, and brain between mice gestated in Hpx or euthyroidism, T cells CD4+CD25+ from spleen have reduced capacity to differentiate in vitro to Treg and to produce IL-10. Thus, our data support the notion that maternal Hpx can imprint the immune response of the offspring suffering EAE probably due to a reduced capacity to trigger suppression. Such "imprints" on the immune system could contribute to explaining as to why adult offspring gestated in Hpx suffer earlier and more intense EAE. © 2018 Haensgen, Albornoz, Opazo, Bugueño, Jara Fernández, Binzberger, Rivero-Castillo, Venegas Salas, Simon, Cabello-Verrugio, Elorza, Kalergis, Bueno and Riedel.https://www.frontiersin.org/articles/10.3389/fimmu.2018.01257/ful