We present the final results from a high sampling rate, multi-month, spectrophotometric reverberation mapping campaign undertaken to obtain either new or improved H{beta} reverberation lag ...measurements for several relatively low-luminosity active galactic nuclei (AGNs). We have reliably measured the time delay between variations in the continuum and H{beta} emission line in six local Seyfert 1 galaxies. These measurements are used to calculate the mass of the supermassive black hole at the center of each of these AGNs. We place our results in context to the most current calibration of the broad-line region (BLR) R{sub BLR}-L relationship, where our results remove outliers and reduce the scatter at the low-luminosity end of this relationship. We also present velocity-resolved H{beta} time-delay measurements for our complete sample, though the clearest velocity-resolved kinematic signatures have already been published.
Selenium (Se) trafficking in oviparous species remains understudied and a major source of uncertainty in developing sound Se regulations. Here, we utilized 75Se to follow Se through a simulated ...natural food chain (water, periphyton, mayflies (Centroptilum triangulifer), fish (Japanese medaka)). We specifically examined Se assimilation efficiency, tissue distribution, efflux rate, and maternal transfer in medaka. Selenium assimilation efficiency (AE) averaged 63.2 ± 8.8% from mayfly diets and was not affected by mayfly Se across a dietary range of 5.6–38.7 μg g–1 (dry wt). However, AE decreased significantly as mayfly larva size increased. Efflux rate constants (k e) were consistent between reproductively inactive (0.066 d–1) and spawning females (0.069 d–1). Total Se loss rate constant (k e+egg; efflux and egg deposition) was 0.17 d–1 in spawning females. Interestingly, medaka appeared to rapidly shuttle Se to their eggs directly from their diet via the ovary, as opposed to mobilization from surrounding tissues, resulting in dynamic egg Se that was more attributable to recent dietary Se ingestion than female whole body Se in this asynchronous spawning fish. Spawning strategy likely plays a large role in the process of fish egg Se deposition and requires further attention to understand risk and toxicity of Se to fish.
A detailed analysis of the data from a high sampling rate, multi-month reverberation mapping campaign, undertaken primarily at MDM Observatory with supporting observations from telescopes around the ...world, reveals that the Hbeta emission region within the broad-line regions (BLRs) of several nearby active galactic nuclei (AGNs) exhibits a variety of kinematic behaviors. While the primary goal of this campaign was to obtain either new or improved Hbeta reverberation lag measurements for several relatively low-luminosity AGNs, we were also able to unambiguously reconstruct velocity-resolved reverberation signals from a subset of our targets. Through high cadence spectroscopic monitoring of the optical continuum and broad Hbeta emission-line variations observed in the nuclear regions of NGC 3227, NGC 3516, and NGC 5548, we clearly see evidence for outflowing, infalling, and virialized BLR gas motions, respectively.
We present the results of a recent reverberation-mapping campaign undertaken to improve measurements of the radius of the broad-line region and the central black hole mass of the quasar PG 2130+099. ...Cross-correlation of the 5100 Aa continuum and H beta emission-line light curves yields a time lag of image days, corresponding to a central black hole mass image. This value supports the notion that previous measurements yielded an incorrect lag. We reanalyze previous data sets to investigate the possible sources of the discrepancy and conclude that previous measurement errors were apparently caused by a combination of undersampling of the light curves and long-term secular changes in the H beta emission-line equivalent width. With our new measurements, PG 2130+099 is no longer an outlier in either the image - L or the image -image relationship.
OJ 287 is a BL Lac object at redshift z= 0.306 that has shown double-peaked bursts at regular intervals of ∼12 yr during the last ∼40 yr. We analyse optical photopolarimetric monitoring data from ...2005 to 2009, during which the latest double-peaked outburst occurred. The aim of this study is twofold: firstly, we aim to analyse variability patterns and statistical properties of the optical polarization light curve. We find a strong preferred position angle in optical polarization. The preferred position angle can be explained by separating the jet emission into two components: an optical polarization core and chaotic jet emission. The optical polarization core is stable on time-scales of years and can be explained as emission from an underlying quiescent jet component. The chaotic jet emission sometimes exhibits a circular movement in the Stokes plane. We find six such events, all on the time-scales of 10–20 d. We interpret these events as a shock front moving forwards and backwards in the jet, swiping through a helical magnetic field. Secondly, we use our data to assess different binary black hole models proposed to explain the regularly appearing double-peaked bursts in OJ 287. We compose a list of requirements a model has to fulfil to explain the mysterious behaviour observed in OJ 287. The list includes not only characteristics of the light curve but also other properties of OJ 287, such as the black hole mass and restrictions on accretion flow properties. We rate all existing models using this list and conclude that none of the models is able to explain all observations. We discuss possible new explanations and propose a new approach to understanding OJ 287. We suggest that both the double-peaked bursts and the evolution of the optical polarization position angle could be explained as a sign of resonant accretion of magnetic field lines, a ‘magnetic breathing’ of the disc.
We present the first results from a high sampling rate, multimonth reverberation mapping campaign undertaken primarily at MDM Observatory with supporting observations from telescopes around the ...world. The primary goal of this campaign was to obtain either new or improved H Delta *b reverberation lag measurements for several relatively low luminosity active galactic nuclei (AGNs). We feature results for NGC 4051 here because, until now, this object has been a significant outlier from AGN scaling relationships, e.g., it was previously a ~2-3 Delta *s outlier on the relationship between the broad-line region (BLR) radius and the optical continuum luminosity-the R BLR-L relationship. Our new measurements of the lag time between variations in the continuum and H Delta *b emission line made from spectroscopic monitoring of NGC 4051 lead to a measured BLR radius of R BLR = 1.87+0.54 -0.50 light days and black hole mass of M BH = (1.73+0.55 -0.52) X 106 M. This radius is consistent with that expected from the R BLR-L relationship, based on the present luminosity of NGC 4051 and the most current calibration of the relation by Bentz et al.. We also present a preliminary look at velocity-resolved H Delta *b light curves and time delay measurements, although we are unable to reconstruct an unambiguous velocity-resolved reverberation signal.
Recent studies from mammalian, fish, and in vitro models have identified bone and cartilage development as sensitive targets for dioxins and other aryl hydrocarbon receptor ligands. In this study, we ...assess how embryonic 2,3,7,8-tetrachlorochlorodibenzo-p-dioxin (TCDD) exposure impacts axial osteogenesis in Japanese medaka (Oryzias latipes), a vertebrate model of human bone development. Embryos from inbred wild-type Orange-red Hd-dR and 3 transgenic medaka lines (twist:EGFP, osx/sp7:mCherry, col10a1:nlGFP) were exposed to 0.15 nM and 0.3 nM TCDD and reared until 20 dpf. Individuals were stained for mineralized bone and imaged using confocal microscopy to assess skeletal alterations in medial vertebrae in combination with a qualitative spatial analysis of osteoblast and osteoblast progenitor cell populations. Exposure to TCDD resulted in an overall attenuation of vertebral ossification characterized by truncated centra, and reduced neural and hemal arch lengths. Effects on mineralization were consistent with modifications in cell number and cell localization of transgene-labeled osteoblast and osteoblast progenitor cells. Endogenous expression of osteogenic regulators runt-related transcription factor 2 (runx2) and osterix (osx/sp7), and extracellular matrix genes osteopontin (spp1), collagen type I alpha I (col1), collagen type X alpha I (col10a1), and osteocalcin (bglap/osc) was significantly diminished at 20 dpf following TCDD exposure as compared with controls. Through global transcriptomic analysis more than 590 differentially expressed genes were identified and mapped to select pathological states including inflammatory disease, connective tissue disorders, and skeletal and muscular disorders. Taken together, results from this study suggest that TCDD exposure inhibits axial bone formation through dysregulation of osteoblast differentiation. This approach highlights the advantages and sensitivity of using small fish models to investigate how xenobiotic exposure may impact skeletal development.
Sulfolane is a solvent used in the petrochemical industry and a groundwater contaminant in areas near refineries. The current studies were conducted to assess the impact of oral exposure to sulfolane ...on the immune system using two models: (1) a perinatal drinking water exposure to 0, 30, 100, 300, or 1000 mg/L from gestation day (GD) 6 until ∼13 weeks-of-age in Harlan Sprague Dawley rats; and, (2) a 90-day gavage exposure of adult female B6C3F1/N mice to 0, 1, 10, 30, 100, or 300 mg/kg/day. Immune parameters evaluated included measurement of antibody production against sheep red blood cells (SRBC) and keyhole limpet hemocyanin (KLH), ex vivo measurements of natural killer (NK) cell activity, cytotoxic T-cell (CTL) activity, and T-cell proliferation, as well as measures of splenic immune cell populations, hematological parameters, and histopathology of immune tissues. A decrease in ex vivo NK cell activity was observed in cells from female - but not male - F1 rats following developmental exposure. In adult female mice, splenic NK cell number was lower than the vehicle controls at doses ≥ 100 mg/kg; however, ex vivo NK cell activity was not affected by sulfolane treatment. In female mice, a decrease in the number of large unstained cells at doses ≥ 30 mg/kg was observed. In F1 rats, effects on white blood cells (WBC) were limited to a decreasing trend in leukocytes in females; no effects were observed in males. Under the conditions of this study, a no-observed-effect level (NOEL) of 3 mg/kg/day was identified based on reduced NK cell activity in female F1 rats. Overall, these findings suggest that oral exposure to sulfolane in rodents had minimal effects on the immune system.
Abstract
Multipotent mesenchymal stem cells (MSCs) maintain the ability to differentiate into adipogenic, chondrogenic, or osteogenic cell lineages. There is increasing concern that exposure to ...environmental agents such as aryl hydrocarbon receptor (AhR) ligands, may perturb the osteogenic pathways responsible for normal bone formation. The objective of the current study was to evaluate the potential of the prototypic AhR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to disrupt osteogenic differentiation of human bone-derived MSCs (hBMSCs) in vitro. Primary hBMSCs from three donors were exposed to 10 nM TCDD and differentiation was interrogated using select histological, biochemical, and transcriptional markers of osteogenesis. Exposure to 10 nM TCDD resulted in an overall consistent attenuation of alkaline phosphatase (ALP) activity and matrix mineralization at terminal stages of differentiation in primary hBMSCs. At the transcriptional level, the transcriptional regulator DLX5 and additional osteogenic markers (ALP, OPN, and IBSP) displayed attenuated expression; conversely, FGF9 and FGF18 were consistently upregulated in each donor. Expression of stem cell potency markers SOX2, NANOG, and SALL4 decreased in the osteogenic controls, whereas expression in TCDD-treated cells resembled that of undifferentiated cells. Coexposure with the AhR antagonist GNF351 blocked TCDD-mediated attenuation of matrix mineralization, and either fully or partially rescued expression of genes associated with osteogenic regulation, extracellular matrix, and/or maintenance of multipotency. Thus, experimental evidence from this study suggests that AhR transactivation likely attenuates osteoblast differentiation in multipotent hBMSCs. This study also underscores the use of primary human MSCs to evaluate osteoinductive or osteotoxic potential of chemical and pharmacologic agents in vitro.
Differentiation of multipotent mesenchymal stem cells (MSCs) into bone-forming osteoblasts requires strict coordination of transcriptional pathways. Aryl hydrocarbon receptor ligands, such as ...2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), have been shown to alter osteoblast differentiation in vitro and bone formation in multiple developmental in vivo models. The goal of the present study was to establish a global transcriptomic landscape during early, intermediate, and apical stages of osteogenic differentiation in vitro in response to TCDD exposure. Human bone-derived mesenchymal stem cells (hBMSCs) were cultured in growth media (GM), osteogenic differentiation media (ODM), or ODM containing 10 nM TCDD (ODM + TCDD), thus enabling a comparison of the transcriptomic profiles of undifferentiated, differentiated, and differentiated-TCDD-exposed hBMSCs, respectively. In this test system, exposure to TCDD attenuated the differentiation of hBMSCs into osteoblasts as evidenced by reduced alkaline phosphatase activity and mineralization. At various timepoints, we observed altered expression of genes that play a role in the Wnt, fibroblast growth factor, bone morphogenetic protein/transforming growth factor beta developmental pathways, as well as pathways related to extracellular matrix organization and deposition. Reconstruction of gene regulatory networks with the interactive dynamic regulatory event miner (iDREM) analysis revealed modulation of transcription factors (TFs) including POLR3G, NR4A1, RDBP, GTF2B, POU2F2, and ZEB1, which may putatively influence osteoblast differentiation and the requisite deposition and mineralization of bone extracellular matrix. We demonstrate that the combination of RNA-Seq data in conjunction with the iDREM regulatory model captures the transcriptional dynamics underlying MSC differentiation under different conditions in vitro. Model predictions are consistent with existing knowledge and provide a new tool to identify novel pathways and TFs that may facilitate a better understanding of the osteoblast differentiation process, perturbation by exogenous agents, and potential intervention strategies targeting those specific pathways.
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