The transcriptome of corona radiata cells from individual MII oocytes that after ICSI developed to embryos selected for transfer: PCOS women compared to healthy women

BACKGROUND: Corona radiata cells (CRCs) refer to the fraction of cumulus cells just adjacent to the oocyte. The CRCs are closely connected to the oocyte throughout maturation and their gene expression profiles might reflect oocyte quality. Polycystic ovary syndrome (PCOS) is a common cause of infertility. It is controversial whether PCOS associate with diminished oocyte quality. The purpose of this study was to compare individual human CRC samples between PCOS patients and controls. METHODS: All patients were stimulated by the long gonadotropin-releasing hormone (GnRH) agonist protocol. The CRC samples originated from individual oocytes developing into embryos selected for transfer. CRCs were isolated in a two-step denudation procedure, separating outer cumulus cells from the inner CRCs. Extracted RNA was amplified and transcriptome profiling was performed with Human Agilent® arrays. RESULTS: The transcriptomes of CRCs showed no individual genes with significant differential expression between PCOS and controls, but gene set enrichment analysis identified several cell cycle- and DNA replication pathways overexpressed in PCOS CRCs (FDR < 0.05). Five of the genes contributing to the up-regulated cell cycle pathways in the PCOS CRCs were selected for qRT-PCR validation in ten PCOS and ten control CRC samples. qRT-PCR confirmed significant up-regulation in PCOS CRCs of cell cycle progression genes HIST1H4C (FC = 2.7), UBE2C (FC = 2.6) and cell cycle related transcription factor E2F4 (FC = 2.5). CONCLUSION: The overexpression of cell cycle-related genes and cell cycle pathways in PCOS CRCs could indicate a disturbed or delayed final maturation and differentiation of the CRCs in response to the human chorionic gonadotropin (hCG) surge. However, this had no effect on the in vitro development of the corresponding embryos. Future studies are needed to clarify whether the up-regulated cell cycle pathways in PCOS CRCs have any clinical implications. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13048-014-0110-6) contains supplementary material, which is available to authorized users

Rashba-type spin splitting at Au(111) beyond the Fermi level: the other part of the story

We present a combined experimental and theoretical study of spin–orbit-induced spin splittings in the unoccupied surface electronic structure of the prototypical Rashba system Au(111). Spin- and angle-resolved inverse-photoemission measurements reveal a Rashba-type spin splitting in the unoccupied part of the L-gap surface state. With increasing momentum parallel to the surface, the spectral intensity is lowered and the spin splitting vanishes as the surface state approaches the band-gap boundary. Furthermore, we observe significantly spin-dependent peak positions and intensities for transitions between unoccupied sp-like bulk bands. Possible reasons for this behavior are considered: initial and final-state effects as well as the transition itself, which is controlled by selection rules depending on the symmetry of the involved states. Based on model calculations, we identify the initial states as origin of the observed Rashba-type spin effects in bulk transitions

Lowering IceCube's energy threshold for point source searches in the Southern Sky

Observation of a point source of astrophysical neutrinos would be a "smoking gun" signature of a cosmic-ray accelerator. While IceCube has recently discovered a diffuse flux of astrophysical neutrinos, no localized point source has been observed. Previous IceCube searches for point sources in the southern sky were restricted by either an energy threshold above a few hundred TeV or poor neutrino angular resolution. Here we present a search for southern sky point sources with greatly improved sensitivities to neutrinos with energies below 100 TeV. By selecting charged-current ν μ interacting inside the detector, we reduce the atmospheric background while retaining efficiency for astrophysical neutrino-induced events reconstructed with sub-degree angular resolution. The new event sample covers three years of detector data and leads to a factor of 10 improvement in sensitivity to point sources emitting below 100 TeV in the southern sky. No statistically significant evidence of point sources was found, and upper limits are set on neutrino emission from individual sources. A posteriori analysis of the highest-energy (~100 TeV) starting event in the sample found that this event alone represents a 2.8σ deviation from the hypothesis that the data consists only of atmospheric background.Fil: Aartsen, M. G.. University of Adelaide; AustraliaFil: Abraham, K.. Technische Universität München; AlemaniaFil: Ackermann, M.. Deutsches Elektronen-Synchrotron; AlemaniaFil: Adams, J.. University Of Canterbury; Nueva ZelandaFil: Aguilar, J. A.. Université Libre de Bruxelles; BélgicaFil: Golup, Geraldina Tamara. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; ArgentinaFil: Wallace, A.. University of Adelaide; AustraliaFil: Wallraff, M.. Rwth Aachen University; AlemaniaFil: Wandkowsky, N.. University of Wisconsin; Estados UnidosFil: Weaver, Ch.. University of Alberta; CanadáFil: Wendt, C.. University of Wisconsin; Estados UnidosFil: Westerhoff, S.. University of Wisconsin; Estados UnidosFil: Whelan, B. J.. University of Adelaide; AustraliaFil: Whitehorn, N.. University of California at Berkeley; Estados UnidosFil: Wickmann, S.. Rwth Aachen University; AlemaniaFil: Wiebe, K.. Johannes Gutenberg Universitat Mainz; AlemaniaFil: Wiebusch, C. H.. Rwth Aachen University; AlemaniaFil: Wille, L.. University of Wisconsin; Estados UnidosFil: Williams, D. R.. University of Alabama at Birmingahm; Estados UnidosFil: Wills, L.. Drexel University; Estados UnidosFil: Wissing, H.. University of Maryland; Estados UnidosFil: Wolf, M.. Stockholms Universitet; SueciaFil: Wood, T. R.. University of Alberta; CanadáFil: Woschnagg, K.. University of California at Berkeley; Estados UnidosFil: Xu, D. L.. University of Wisconsin; Estados UnidosFil: Xu, X. W.. Southern University; Estados UnidosFil: Xu, Y.. Stony Brook University; Estados UnidosFil: Yanez, J. P.. Deutsches Elektronen-Synchrotron; AlemaniaFil: Yodh, G.. University of California at Irvine; Estados UnidosFil: Yoshida, S.. Chiba University; JapónFil: Zoll, M.. Stockholms Universitet; Sueci

Ultra-Relativistic Magnetic Monopole Search with the ANITA-II Balloon-borne Radio Interferometer

We have conducted a search for extended energy deposition trails left by ultra-relativistic magnetic monopoles interacting in Antarctic ice. The non-observation of any satisfactory candidates in the 31 days of accumulated ANITA-II flight data results in an upper limit on the diffuse flux of relativistic monopoles. We obtain a 90% C.L. limit of order 10^{-19}/(cm^2-s-sr) for values of Lorentz boost factor 10^{10}<gamma at the anticipated energy E=10^{16} GeV. This bound is stronger than all previously published experimental limits for this kinematic range.Comment: updated to version accepted by Phys. Rev.

Conversion to sirolimus for chronic renal allograft dysfunction: risk factors for graft loss and severe side effects

We retrospectively reviewed our experience with 45 kidney transplant recipients (KTR) that were switched from CNI to SRL, mainly for chronic allograft dysfunction (CAD) (41/45). The mean serum creatinine at switch was 2.5 ± 0.8 mg/dl. At 1 year, patient survival was 93%. Death-censored graft survival was 67% at 1 year and 54% at 2 years. SRL was stopped because of severe side effects in 15 patients. Among these, eight patients developed ‘de novo’ high-grade proteinuria. Univariate analysis revealed that (1) a higher SRL level at 1 month was a predictor of SRL withdrawal due to severe side effects (P = 0.006), and (2) predictors of graft failure after SRL conversion were low SRL loading dose (P = 0.03) and a higher creatinine level at conversion (P = 0.003)

Effect of Mechanical Stimuli on the Phenotypic Plasticity of Induced Pluripotent Stem-Cell-Derived Vascular Smooth Muscle Cells in a 3D Hydrogel

Introduction: Vascular smooth muscle cells (VSMCs) play a pivotal role in vascular homeostasis, with dysregulation leading to vascular complications. Human-induced pluripotent stem-cell (hiPSC)-derived VSMCs offer prospects for personalized disease modeling and regenerative strategies. Current research lacks comparative studies on the impact of three-dimensional (3D) substrate properties under cyclic strain on phenotypic adaptation in hiPSC-derived VSMCs. Here, we aim to investigate the impact of intrinsic substrate properties, such as the hydrogel’s elastic modulus and cross-linking density in a 3D static and dynamic environment, on the phenotypical adaptation of human mural cells derived from hiPSC-derived organoids (ODMCs), compared to aortic VSMCs. Methods and results: ODMCs were cultured in two-dimensional (2D) conditions with synthetic or contractile differentiation medium or in 3D Gelatin Methacryloyl (GelMa) substrates with varying degrees of functionalization and percentages to modulate Young’s modulus and cross-linking density. Cells in 3D substrates were exposed to cyclic, unidirectional strain. Phenotype characterization was conducted using specific markers through immunofluorescence and gene expression analysis. Under static 2D culture, ODMCs derived from hiPSCs exhibited a VSMC phenotype, expressing key mural markers, and demonstrated a level of phenotypic plasticity similar to primary human VSMCs. In static 3D culture, a substrate with a higher Young’s modulus and cross-linking density promoted a contractile phenotype in ODMCs and VSMCs. Dynamic stimulation in the 3D substrate promoted a switch toward a contractile phenotype in both cell types. Conclusion: Our study demonstrates phenotypic plasticity of human ODMCs in response to 2D biological and 3D mechanical stimuli that equals that of primary human VSMCs. These findings may contribute to the advancement of tailored approaches for vascular disease modeling and regenerative strategies.</p

Search for Point Sources of High Energy Neutrinos with AMANDA

This paper describes the search for astronomical sources of high-energy neutrinos using the AMANDA-B10 detector, an array of 302 photomultiplier tubes, used for the detection of Cherenkov light from upward traveling neutrino-induced muons, buried deep in ice at the South Pole. The absolute pointing accuracy and angular resolution were studied by using coincident events between the AMANDA detector and two independent telescopes on the surface, the GASP air Cherenkov telescope and the SPASE extensive air shower array. Using data collected from April to October of 1997 (130.1 days of livetime), a general survey of the northern hemisphere revealed no statistically significant excess of events from any direction. The sensitivity for a flux of muon neutrinos is based on the effective detection area for through-going muons. Averaged over the Northern sky, the effective detection area exceeds 10,000 m^2 for E_{mu} ~ 10 TeV. Neutrinos generated in the atmosphere by cosmic ray interactions were used to verify the predicted performance of the detector. For a source with a differential energy spectrum proportional to E_{nu}^{-2} and declination larger than +40 degrees, we obtain E^2(dN_{nu}/dE) <= 10^{-6}GeVcm^{-2}s^{-1} for an energy threshold of 10 GeV.Comment: 46 pages, 22 figures, 4 tables, submitted to Ap.

Limits on diffuse fluxes of high energy extraterrestrial neutrinos with the AMANDA-B10 detector

Data from the AMANDA-B10 detector taken during the austral winter of 1997 have been searched for a diffuse flux of high energy extraterrestrial muon-neutrinos, as predicted from, e.g., the sum of all active galaxies in the universe. This search yielded no excess events above those expected from the background atmospheric neutrinos, leading to upper limits on the extraterrestrial neutrino flux. For an assumed E^-2 spectrum, a 90% classical confidence level upper limit has been placed at a level E^2 Phi(E) = 8.4 x 10^-7 GeV cm^-2 s^-1 sr^-1 (for a predominant neutrino energy range 6-1000 TeV) which is the most restrictive bound placed by any neutrino detector. When specific predicted spectral forms are considered, it is found that some are excluded.Comment: Submitted to Physical Review Letter

HEPPA III Intercomparison Experiment on Electron Precipitation Impacts: 1. Estimated Ionization Rates During a Geomagnetic Active Period in April 2010

Precipitating auroral and radiation belt electrons are considered an important part of the natural forcing of the climate system. Recent studies suggest that this forcing is underestimated in current chemistry-climate models. The High Energy Particle Precipitation in the Atmosphere III intercomparison experiment is a collective effort to address this point. Here, eight different estimates of medium energy electron (MEE) (urn:x-wiley:21699380:media:jgra56926:jgra56926-math-0001) ionization rates are assessed during a geomagnetic active period in April 2010. The objective is to understand the potential uncertainty related to the MEE energy input. The ionization rates are all based on the Medium Energy Proton and Electron Detector (MEPED) on board the NOAA/POES and EUMETSAT/MetOp spacecraft series. However, different data handling, ionization rate calculations, and background atmospheres result in a wide range of mesospheric electron ionization rates. Although the eight data sets agree well in terms of the temporal variability, they differ by about an order of magnitude in ionization rate strength both during geomagnetic quiet and disturbed periods. The largest spread is found in the aftermath of enhanced geomagnetic activity. Furthermore, governed by different energy limits, the atmospheric penetration depth varies, and some differences related to latitudinal coverage are also evident. The mesospheric NO densities simulated with the Whole Atmospheric Community Climate Model driven by highest and lowest ionization rates differ by more than a factor of eight. In a follow-up study, the atmospheric responses are simulated in four chemistry-climate models (CCM) and compared to satellite observations, considering both the CCM structure and the ionization forcing