Decreased Specific Star Formation Rates in AGN Host Galaxies

We investigate the location of an ultra-hard X-ray selected sample of AGN from the Swift Burst Alert Telescope (BAT) catalog with respect to the main sequence (MS) of star-forming galaxies using Herschel-based measurements of the star formation rate (SFR) and stellar mass (\mstar) from Sloan Digital Sky Survey (SDSS) photometry where the AGN contribution has been carefully removed. We construct the MS with galaxies from the Herschel Reference Survey and Herschel Stripe 82 Survey using the exact same methods to measure the SFR and \mstar{} as the Swift/BAT AGN. We find a large fraction of the Swift/BAT AGN lie below the MS indicating decreased specific SFR (sSFR) compared to non-AGN galaxies. The Swift/BAT AGN are then compared to a high-mass galaxy sample (COLD GASS), where we find a similarity between the AGN in COLD GASS and the Swift/BAT AGN. Both samples of AGN lie firmly between star-forming galaxies on the MS and quiescent galaxies far below the MS. However, we find no relationship between the X-ray luminosity and distance from the MS. While the morphological distribution of the BAT AGN is more similar to star-forming galaxies, the sSFR of each morphology is more similar to the COLD GASS AGN. The merger fraction in the BAT AGN is much higher than the COLD GASS AGN and star-forming galaxies and is related to distance from the MS. These results support a model in which bright AGN tend to be in high mass star-forming galaxies in the process of quenching which eventually starves the supermassive black hole itself.Comment: 23 pages, 14 figures, Accepted for publication in MNRAS 2015 June 23. In original form 2015 January 2

Optical Spectral Properties of Swift BAT Hard X-ray Selected Active Galactic Nuclei Sources

The Swift Burst Alert Telescope (BAT) survey of Active Galactic Nuclei (AGN) is providing an unprecedented view of local AGNs ( = 0.03) and their host galaxy properties. In this paper, we present an analysis of the optical spectra of a sample of 64 AGNs from the 9-month survey, detected solely based on their 14-195 keV flux. Our analysis includes both archived spectra from the Sloan Digital Sky Survey and our own observations from the 2.1-m Kitt Peak National Observatory telescope. Among our results, we include line ratio classifications utilizing standard emission line diagnostic plots, [O III] 5007 A luminosities, and H-beta derived black hole masses. As in our X-ray study, we find the type 2 sources to be less luminous (in [O III] 5007 A and 14-195 keV luminosities) with lower accretion rates than the type 1 sources. We find that the optically classified LINERs, H II/composite galaxies, and ambiguous sources have the lowest luminosities, while both broad line and narrow line Seyferts have similar luminosities. From a comparison of the hard X-ray (14-195 keV) and [O III] luminosities, we find that both the observed and extinction-corrected [O III] luminosities are weakly correlated with X-ray luminosity. In a study of the host galaxy properties from both continuum fits and measurements of the stellar absorption indices, we find that the hosts of the narrow line sources have properties consistent with late type galaxies.Comment: 84 pages, 20 figures, 17 tables, accepted in Ap

Quantifying Isoniazid Levels in Small Hair Samples: A Novel Method for Assessing Adherence during the Treatment of Latent and Active Tuberculosis.

BackgroundTuberculosis (TB) is the leading cause of death from an infectious pathogen worldwide and the most prevalent opportunistic infection in people living with HIV. Isoniazid preventive therapy (IPT) reduces the incidence of active TB and reduces morbidity and mortality in HIV-infected patients independently of antiretroviral therapy. However, treatment of latent or active TB is lengthy and inter-patient variability in pharmacokinetics and adherence common. Current methods of assessing adherence to TB treatment using drug levels in plasma or urine assess short-term exposure and pose logistical challenges. Drug concentrations in hair assess long-term exposure and have demonstrated pharmacodynamic relevance in HIV.MethodsA large hair sample from a patient with active TB was obtained for assay development. Methods to pulverize hair and extract isoniazid were optimized and then the drug detected by liquid chromatography/ tandem mass spectrometry (LC/MS-MS). The method was validated for specificity, accuracy, precision, recovery, linearity and stability to establish the assay's suitability for therapeutic drug monitoring (TDM). Hair samples from patients on directly-observe isoniazid-based latent or active TB therapy from the San Francisco Department of Public Health TB clinic were then tested.ResultsOur LC/MS-MS-based assay detected isoniazid in quantities as low as 0.02ng/mg using 10-25 strands hair. Concentrations in spiked samples demonstrated linearity from 0.05-50ng/mg. Assay precision and accuracy for spiked quality-control samples were high, with an overall recovery rate of 79.5%. In 18 patients with latent or active TB on treatment, isoniazid was detected across a wide linear dynamic range.ConclusionsAn LC-MS/MS-based assay to quantify isoniazid levels in hair with performance characteristics suitable for TDM was developed and validated. Hair concentrations of isoniazid assess long-term exposure and may be useful for monitoring adherence to latent or active TB treatment in the setting of HIV

Composition of bioactive secondary metabolites and mutagenicity of Sambucus nigra L. Fruit at different stages of ripeness

The relationship between the content of bioactive compounds and mutagenic activity of elderberry fruit at different stages of ripeness was investigated. Significant differences in the antioxidant profiles (TLC, HPLC with post-column derivatization) and antioxidant activity (ABTS, DPPH, and FC tests) were observed for studied elderberry extracts. The more ripen the fruit at the time of harvest were, the higher the content of anthocyanins (increase from 0 to 7.8 mg g−1d.w.) and antioxidant activity of the extracts (about 5-fold increase) were. Cyanogenic glycosides were not detected at any stage of ripeness. Accordingly, Ames MPF test (Xenometrix) did not reveal any mutagenicity. Our study suggests that instability of cyanogenic glycosides ensures safety of food/pharmaceutical products based on even not fully ripen elderberry fruit

Decreased specific star formation rates in AGN host galaxies

We investigate the location of an ultra-hard X-ray selected sample of active galactic nuclei (AGN) from the Swift Burst Alert Telescope (BAT) catalogue with respect to the main sequence (MS) of star-forming galaxies using Herschel-based measurements of the star formation rate (SFR) and M*'s from Sloan Digital Sky Survey photometry where the AGN contribution has been carefully removed. We construct the MS with galaxies from the Herschel Reference Survey and Herschel Stripe 82 Survey using the exact same methods to measure the SFR and M* as the Swift/BAT AGN. We find that a large fraction of the Swift/BAT AGN lie below the MS indicating decreased specific SFR (sSFR) compared to non-AGN galaxies. The Swift/BAT AGN are then compared to a high-mass galaxy sample (CO Legacy Database for GALEX Arecibo SDSS Survey, COLD GASS), where we find a similarity between the AGN in COLD GASS and the Swift/BAT AGN. Both samples of AGN lie firmly between star-forming galaxies on the MS and quiescent galaxies far below the MS. However, we find no relationship between the X-ray luminosity and distance from the MS. While the morphological distribution of the BAT AGN is more similar to star-forming galaxies, the sSFR of each morphology is more similar to the COLD GASS AGN. The merger fraction in the BAT AGN is much higher than the COLD GASS AGN and star-forming galaxies and is related to distance from the MS. These results support a model in which bright AGN tend to be in high-mass star-forming galaxies in the process of quenching which eventually starves the supermassive black hole itsel

Optimizing urothelial cell preparation for the human urinary micronucleus assay

Biological monitoring of early genotoxic effects in urothelial cells using the urinary micronucleus (MNu) assay is promising for early detection of cancer, such as bladder carcinoma. But many problems are encountered, the major being the poorly differential staining of cells, particularly in women having an important amount of squamous cells. We have optimized the protocol and obtained a differential staining of the cell types present in urine on 10 subjects. Following Carnoy I fixation and Papanicolaou staining, urothelial cells were blue while most squamous cells were pink. This differential staining allowed for optimization of the MNu assay on a single urine void, for both females and males. Even if our MNu means were comparable to the literature, the great variation in reported MNu results could reside in the ability of scorers to distinguish correctly between urothelial and squamous cells. When monitoring exposed populations, this erroneous distinction could largely influence the results, even more in women’s urine samples. Given a situation where exposure would not increase micronuclei frequency in vaginal squamous cells, their erroneous analysis in the MNu assay could mask an early genotoxic effect. Therefore, as transitional cell carcinoma of the bladder originates from transformed urothelial cells, restricting micronuclei analysis to urothelial cells could yield a more precise estimate of cancer risk in exposed populations. Moreover, it is hoped that the improvements proposed in this paper will allow for an easier implementation of the MNu assay in various set-ups and enhance its specificity, since MNu are considered a suitable biomarker

Design, synthesis, and evaluation of peptide-imidazo[1,2-a]pyrazine bioconjugates as potential bivalent inhibitors of the VirB11 ATPase HP0525

Helicobacter pylori (H. pylori) infections have been implicated in the development of gastric ulcers and various cancers: however, the success of current therapies is compromised by rising antibiotic resistance. The virulence and pathogenicity of H. pylori is mediated by the type IV secretion system (T4SS), a multiprotein macromolecular nanomachine that transfers toxic bacterial factors and plasmid DNA between bacterial cells, thus contributing to the spread of antibiotic resistance. A key component of the T4SS is the VirB11 ATPase HP0525, which is a hexameric protein assembly. We have previously reported the design and synthesis of a series of novel 8-amino imidazo[1,2-a]pyrazine derivatives as inhibitors of HP0525. In order to improve their selectivity, and potentially develop these compounds as tools for probing the assembly of the HP0525 hexamer, we have explored the design and synthesis of potential bivalent inhibitors. We used the structural details of the subunit-subunit interactions within the HP0525 hexamer to design peptide recognition moieties of the subunit interface. Different methods (cross metathesis, click chemistry, and cysteine-malemide) for bioconjugation to selected 8-amino imidazo[1,2-a]pyrazines were explored, as well as peptides spanning larger or smaller regions of the interface. The IC50 values of the resulting linker-8-amino imidazo[1,2-a]pyrazine derivatives, and the bivalent inhibitors, were related to docking studies with the HP0525 crystal structure and to molecular dynamics simulations of the peptide recognition moieties