Loss of Endometrial Plasticity in Recurrent Pregnancy Loss

© 2015 AlphaMed Press.Menstruation drives cyclic activation of endometrial progenitor cells, tissue regeneration, and maturation of stromal cells, which differentiate into specialized decidual cells prior to and during pregnancy. Aberrant responsiveness of human endometrial stromal cells (HESCs) to deciduogenic cues is strongly associated with recurrent pregnancy loss (RPL), suggesting a defect in cellular maturation. MeDIP-seq analysis of HESCs did not reveal gross perturbations in CpG methylation in RPL cultures, although quantitative differences were observed in or near genes that are frequently deregulated in vivo. However, RPL was associated with a marked reduction in methylation of defined CA-rich motifs located throughout the genome but enriched near telomeres. Non-CpG methylation is a hallmark of cellular multipotency. Congruently, we demonstrate that RPL is associated with a deficiency in endometrial clonogenic cell populations. Loss of epigenetic stemness features also correlated with intragenic CpG hypomethylation and reduced expression of HMGB2, coding high mobility group protein 2. We show that knockdown of this sequence-independent chromatin protein in HESCs promotes senescence and impairs decidualization, exemplified by blunted time-dependent secretome changes. Our findings indicate that stem cell deficiency and accelerated stromal senescence limit the differentiation capacity of the endometrium and predispose for pregnancy failure. Stem Cells 2016;34:346-356 Recurrent pregnancy loss is caused by endometrial stem cell deficiency, triggering heightened tissue senescence and impaired decidualization

Uterine selection of human embryos at implantation

Human embryos frequently harbor large-scale complex chromosomal errors that impede normal development. Affected embryos may fail to implant although many first breach the endometrial epithelium and embed in the decidualizing stroma before being rejected via mechanisms that are poorly understood. Here we show that developmentally impaired human embryos elicit an endoplasmic stress response in human decidual cells. A stress response was also evident upon in vivo exposure of mouse uteri to culture medium conditioned by low-quality human embryos. By contrast, signals emanating from developmentally competent embryos activated a focused gene network enriched in metabolic enzymes and implantation factors. We further show that trypsin, a serine protease released by pre-implantation embryos, elicits Ca2+ signaling in endometrial epithelial cells. Competent human embryos triggered short-lived oscillatory Ca2+ fluxes whereas low-quality embryos caused a heightened and prolonged Ca2+ response. Thus, distinct positive and negative mechanisms contribute to active selection of human embryos at implantation

Calibration of photomultiplier arrays

A method is described that allows calibration and assessment of the linearity of response of an array of photomultiplier tubes. The method does not require knowledge of the photomultiplier single photoelectron response model and uses science data directly, thus eliminating the need for dedicated data sets. In this manner all photomultiplier working conditions (e.g. temperature, external fields, etc.) are exactly matched between calibration and science acquisitions. This is of particular importance in low background experiments such as ZEPLIN-III, where methods involving the use of external light sources for calibration are severely constrained

Limits on the spin-dependent WIMP-nucleon cross-sections from the first science run of the ZEPLIN-III experiment

We present new experimental constraints on the WIMP-nucleon spin-dependent elastic cross-sections using data from the first science run of ZEPLIN-III, a two-phase xenon experiment searching for galactic dark matter WIMPs based at the Boulby mine. Analysis of $\sim$450 kg$\cdot$days fiducial exposure revealed a most likely signal of zero events, leading to a 90%-confidence upper limit on the pure WIMP-neutron cross-section of $\sigma_n=1.8\times 10^{-2}$ pb at 55 GeV/$c^2$ WIMP mass. Recent calculations of the nuclear spin structure based on the Bonn CD nucleon-nucleon potential were used for the odd-neutron isotopes $^{129}$Xe and $^{131}$Xe. These indicate that the sensitivity of xenon targets to the spin-dependent WIMP-proton interaction is much lower than implied by previous calculations, whereas the WIMP-neutron sensitivity is impaired only by a factor of $\sim$2

Measurement and simulation of the muon-induced neutron yield in lead

A measurement is presented of the neutron production rate in lead by high energy cosmic-ray muons at a depth of 2850 m water equivalent (w.e.) and a mean muon energy of 260 GeV. The measurement exploits the delayed coincidences between muons and the radiative capture of induced neutrons in a highly segmented tonne scale plastic scintillator detector. Detailed Monte Carlo simulations reproduce well the measured capture times and multiplicities and, within the dynamic range of the instrumentation, the spectrum of energy deposits. By comparing measurements with simulations of neutron capture rates a neutron yield in lead of (View the MathML source) ×10-3 neutrons/muon/(g/cm2) has been obtained. Absolute agreement between simulation and data is of order 25%. Consequences for deep underground rare event searches are discussed

The Very Energetic Radiation Imaging Telescope Array System (VERITAS)

We give an overview of the current status and scientific goals of VERITAS, a proposed hexagonal array of seven 10 m aperture imaging Cherenkov telescopes. The selected site is Montosa Canyon (1390 m a.s.l.) at the Whipple Observatory, Arizona. Each telescope, of 12 m focal length, will initially be equipped with a 499 element photomultiplier camera covering a 3.5 degree field of view. A central station will initiate the readout of 500 MHz FADCs upon receipt of multiple telescope triggers. The minimum detectable flux sensitivity will be 0.5% of the Crab Nebula flux at 200 GeV. Detailed simulations of the array's performance are presented elsewhere at this meeting. VERITAS will operate primarily as a gamma-ray observatory in the 50 GeV to 50 TeV range for the study of active galaxies, supernova remnants, pulsars and gamma-ray bursts

Transient heliosheath modulation

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Numerical simulation of test particle diffusive shock acceleration in relativistic shocks with application to AGN 'central engines'

Numerical modelling is performed for extreme relativistic parallel shocks with upstream Lorentz factors Gamma = 50. Assuming that the scattering is either large-angle or over pitch angles > Gamma(-1), spectral flattening and shock acceleration speed-up is found. The energy gain per cycle is similar to Gamma(2). The likely output from relativistic shocks due to the infall from the accretion disc to the AGN black hole is computed. Neutrinos from proton-gamma interactions may be detectable with planned neutrino telescopes but the gamma-ray output may contribute only 1/100th of the observed flux of 3C 273