Cytochrome P4501A induction in avian hepatocyte cultures exposed to polychlorinated biphenyls: comparisons with AHR1-mediated reporter gene activity and in ovo toxicity.

Avian-specific toxic equivalency factors (TEFs) were developed by the World Health Organization to simplify environmental risk assessments of dioxin-like compounds (DLCs), but TEFs do not account for differences in the toxic and biochemical potencies of DLCs among species of birds. Such variability may be due to differences in species sensitivity to individual DLCs. The sensitivity of avian species to DLCs was recently associated with the identity of amino acids 324 and 380 in the aryl hydrocarbon receptor 1 (AHR1) ligand binding domain. A luciferase reporter gene (LRG) assay, measuring AHR1-mediated induction of a cytochrome P450 1A5 (CYP1A5) reporter gene, in combination with a species' AHR1 ligand binding domain sequence, were also shown to predict avian species sensitivity to polychlorinated biphenyls (PCBs) and PCB relative potency in a given species. The goals of the present study were to (1) characterize the concentration-dependent effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin and PCBs 126, 77, 105 and 118 on induction of ethoxyresorufin O-deethylase (EROD) activity and CYP1A4/5 mRNA in chicken, ring-necked pheasant and Japanese quail embryo hepatocytes and (2) compare these in vitro results to those previously generated by the LRG assay and in ovo toxicity studies. EROD activity and CYP1A4/5 mRNA expression data support and complement the findings of the LRG assay. CYP1A enzyme activity and mRNA expression were significantly correlated both with luciferase activity and in ovo toxicity induced by PCBs. Relative potency values were generally similar between the LRG and EROD assays and indicate that the relative potency of some PCBs may differ among species.

A luciferase reporter gene assay and aryl hydrocarbon receptor 1 genotype predict the LD50 of polychlorinated biphenyls in avian species.

Birds differ in sensitivity to the embryotoxic effects of polychlorinated biphenyls (PCBs), which complicates environmental risk assessments for these chemicals. Recent research has shown that the identities of amino acid residues 324 and 380 in the avian aryl hydrocarbon receptor 1 (AHR1) ligand binding domain (LBD) are primarily responsible for differences in avian species sensitivity to selected dibenzo-p-dioxins and furans. A luciferase reporter gene (LRG) assay was developed in our laboratory to measure AHR1-mediated induction of a cytochrome P450 1A5 reporter gene in COS-7 cells transfected with different avian AHR1 constructs. In the present study, the LRG assay was used to measure the concentration-dependent effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and PCBs 126, 77, 105 and 118 on luciferase activity in COS-7 cells transfected with AHR1 constructs representative of 86 avian species in order to predict their sensitivity to PCB-induced embryolethality and the relative potency of PCBs in these species. The results of the LRG assay indicate that the identity of amino acid residues 324 and 380 in the AHR1 LBD are the major determinants of avian species sensitivity to PCBs. The relative potency of PCBs did not differ greatly among AHR1 constructs. Luciferase activity was significantly correlated with embryolethality data obtained from the literature (R(2)≥0.87, p<0.0001). Thus, the LRG assay in combination with the knowledge of a species' AHR1 LBD sequence can be used to predict PCB-induced embryolethality in potentially any avian species of interest without the use of lethal methods on a large number of individuals.

Detection of the power spectrum of cosmic microwave background lensing by the Atacama Cosmology Telescope.

We report the first detection of the gravitational lensing of the cosmic microwave background through a measurement of the four-point correlation function in the temperature maps made by the Atacama Cosmology Telescope. We verify our detection by calculating the levels of potential contaminants and performing a number of null tests. The resulting convergence power spectrum at 2° angular scales measures the amplitude of matter density fluctuations on comoving length scales of around 100 Mpc at redshifts around 0.5 to 3. The measured amplitude of the signal agrees with Lambda cold dark matter cosmology predictions. Since the amplitude of the convergence power spectrum scales as the square of the amplitude of the density fluctuations, the 4σ detection of the lensing signal measures the amplitude of density fluctuations to 12%.

Evidence for dark energy from the cosmic microwave background alone using the Atacama Cosmology Telescope lensing measurements.

For the first time, measurements of the cosmic microwave background radiation (CMB) alone favor cosmologies with w = -1 dark energy over models without dark energy at a 3.2-sigma level. We demonstrate this by combining the CMB lensing deflection power spectrum from the Atacama Cosmology Telescope with temperature and polarization power spectra from the Wilkinson Microwave Anisotropy Probe. The lensing data break the geometric degeneracy of different cosmological models with similar CMB temperature power spectra. Our CMB-only measurement of the dark energy density Ω(Λ) confirms other measurements from supernovae, galaxy clusters, and baryon acoustic oscillations, and demonstrates the power of CMB lensing as a new cosmological tool.

Over half of the far-infrared background light comes from galaxies at z >or= 1.2.

Submillimetre surveys during the past decade have discovered a population of luminous, high-redshift, dusty starburst galaxies. In the redshift range 1 or= 1.2 accounting for 70% of it. As expected, at the longest wavelengths the signal is dominated by ultraluminous galaxies at z > 1.

Structural characterization and thermal stabilities of the isomers of the brominated flame retardant 1,2,5,6-tetrabromocyclooctane (TBCO).

1,2,5,6-Tetrabromocyclooctane (TBCO) is a commercial brominated flame retardant that is employed mainly as an additive in textiles, paints and plastics. Very little is known about its presence or behavior in the environment or its analysis. TBCO can exist as two diastereomers, the stereochemistries of which have not been previously reported. We have named the first eluting isomer, under HPLC conditions, as alpha-TBCO (alpha-TBCO) and the later eluting isomer as beta-TBCO (beta-TBCO) when using an Acquity UPLC BEH C(18) column with methanol/acetonitrile/water as the mobile phase. The structural elucidation of these two isomers was accomplished by 1H NMR spectroscopy, GC/MS, LC/MS and X-ray structure determinations. alpha-TBCO is (1R,2R,5S,6S)-1,2,5,6-tetrabromocyclooctane and beta-TBCO is rac-(1R,2R,5R,6R)-1,2,5,6-tetrabromocyclooctane. As with some other brominated cycloaliphatic compounds, TBCO is thermally labile and the isomers easily interconvert. A thermal equilibrium mixture of alpha- and beta-TBCO consists of approximately 15% and 85% of these isomers, respectively. Separation of the two diastereomers, with minimal thermal interconversion between them, is achievable by careful selection of GC-capillary column length and injector temperature. LC/MS analyses of TBCO also presents an analytical challenge due to poor resolution of the isomers on chromatographic stationary phases, and weak intensity of molecular ions (or major fragment ions) when using LC-ESI/MS. Only bromide ions were seen in the mass spectra. APCI and APPI also failed to produce the molecular ion with sufficient intensity for identification.

Successive pregnancies with delivery of two healthy infants in a couple who was discordant for human immunodeficiency virus infection.

OBJECTIVE: To describe two successive pregnancies resulting in two healthy infants in an HIV-discordant couple who underwent IVF-ICSI. DESIGN: Case report. SETTING: University-based infertility clinic. PATIENT(S): A couple seeking fertility treatment in which the male partner was seropositive for HIV-1. INTERVENTION(S): Controlled ovarian hyperstimulation and IVF-ET with ICSI. MAIN OUTCOME MEASURE(S): Pregnancy outcome and HIV-1 seroconversion. RESULT(S): The couple delivered two healthy infants on successive pregnancies with use of IVF-ET with ICSI. CONCLUSION(S): For HIV-discordant couples in which the male partner is seropositive for HIV-1, IVF with ICSI is a viable option.