Theoretical calculation of photodetachment intensities for H3O−

This is the publisher's version, also available electronically from http://scitation.aip.org/content/aip/journal/jcp/105/13/10.1063/1.472380.We have calculated total and arrangement‐selected photodetachment intensities for the H3O− anion (and its deuterated form, D3O−) using a Green’s function in a discrete variable representation with absorbing boundary conditions. A multiply‐shifted quasiminimal residual method is used to obtain the Green’s function for many energies at once. We present spectra obtained by explicitly treating two and four degrees of freedom. Comparison with experiment indicates that the bending angles in the anion and neutral are more similar than in the current potential energy surfaces. The calculated spectra are also consistent with the suggestion that the barrier should be ‘‘earlier.’

Hepatic Xenobiotic Metabolizing Enzyme and Transporter Gene Expression through the Life Stages of the Mouse

Differences in responses to environmental chemicals and drugs between life stages are likely due in part to differences in the expression of xenobiotic metabolizing enzymes and transporters (XMETs). No comprehensive analysis of the mRNA expression of XMETs has been carried out through life stages in any species.Using full-genome arrays, the mRNA expression of all XMETs and their regulatory proteins was examined during fetal (gestation day (GD) 19), neonatal (postnatal day (PND) 7), prepubescent (PND32), middle age (12 months), and old age (18 and 24 months) in the C57BL/6J (C57) mouse liver and compared to adults. Fetal and neonatal life stages exhibited dramatic differences in XMET mRNA expression compared to the relatively minor effects of old age. The total number of XMET probe sets that differed from adults was 636, 500, 84, 5, 43, and 102 for GD19, PND7, PND32, 12 months, 18 months and 24 months, respectively. At all life stages except PND32, under-expressed genes outnumbered over-expressed genes. The altered XMETs included those in all of the major metabolic and transport phases including introduction of reactive or polar groups (Phase I), conjugation (Phase II) and excretion (Phase III). In the fetus and neonate, parallel increases in expression were noted in the dioxin receptor, Nrf2 components and their regulated genes while nuclear receptors and regulated genes were generally down-regulated. Suppression of male-specific XMETs was observed at early (GD19, PND7) and to a lesser extent, later life stages (18 and 24 months). A number of female-specific XMETs exhibited a spike in expression centered at PND7.The analysis revealed dramatic differences in the expression of the XMETs, especially in the fetus and neonate that are partially dependent on gender-dependent factors. XMET expression can be used to predict life stage-specific responses to environmental chemicals and drugs

Toxicogenomic analysis incorporating operon-transcriptional coupling and toxicant concentration-expression response: analysis of MX-treated Salmonella

<p>Abstract</p> <p>Background</p> <p>Deficiencies in microarray technology cause unwanted variation in the hybridization signal, obscuring the true measurements of intracellular transcript levels. Here we describe a general method that can improve microarray analysis of toxicant-exposed cells that uses the intrinsic power of transcriptional coupling and toxicant concentration-expression response data. To illustrate this approach, we characterized changes in global gene expression induced in <it>Salmonella typhimurium </it>TA100 by 3-chloro-4-(dichloromethyl)-5-hydroxy-2(<it>5H</it>)-furanone (MX), the primary mutagen in chlorinated drinking water. We used the co-expression of genes within an operon and the monotonic increases or decreases in gene expression relative to increasing toxicant concentration to augment our identification of differentially expressed genes beyond Bayesian-t analysis.</p> <p>Results</p> <p>Operon analysis increased the number of altered genes by 95% from the list identified by a Bayesian t-test of control to the highest concentration of MX. Monotonic analysis added 46% more genes. A functional analysis of the resulting 448 differentially expressed genes yielded functional changes beyond what would be expected from only the mutagenic properties of MX. In addition to gene-expression changes in DNA-damage response, MX induced changes in expression of genes involved in membrane transport and porphyrin metabolism, among other biological processes. The disruption of porphyrin metabolism might be attributable to the structural similarity of MX, which is a chlorinated furanone, to ligands indigenous to the porphyrin metabolism pathway. Interestingly, our results indicate that the <it>lexA </it>regulon in <it>Salmonella</it>, which partially mediates the response to DNA damage, may contain only 60% of the genes present in this regulon in <it>E. coli</it>. In addition, <it>nanH </it>was found to be highly induced by MX and contains a putative <it>lexA </it>regulatory motif in its regulatory region, suggesting that it may be regulated by <it>lexA</it>.</p> <p>Conclusion</p> <p>Operon and monotonic analyses improved the determination of differentially expressed genes beyond that of Bayesian-t analysis, showing that MX alters cellular metabolism involving pathways other than DNA damage. Because co-expression of similarly functioning genes also occurs in eukaryotes, this method has general applicability for improving analysis of toxicogenomic data.</p

Transcriptional ontogeny of the developing liver

<p>Abstract</p> <p>Background</p> <p>During embryogenesis the liver is derived from endodermal cells lining the digestive tract. These endodermal progenitor cells contribute to forming the parenchyma of a number of organs including the liver and pancreas. Early in organogenesis the fetal liver is populated by hematopoietic stem cells, the source for a number of blood cells including nucleated erythrocytes. A comprehensive analysis of the transcriptional changes that occur during the early stages of development to adulthood in the liver was carried out.</p> <p>Results</p> <p>We characterized gene expression changes in the developing mouse liver at gestational days (GD) 11.5, 12.5, 13.5, 14.5, 16.5, and 19 and in the neonate (postnatal day (PND) 7 and 32) compared to that in the adult liver (PND67) using full-genome microarrays. The fetal liver, and to a lesser extent the neonatal liver, exhibited dramatic differences in gene expression compared to adults. Canonical pathway analysis of the fetal liver signature demonstrated increases in functions important in cell replication and DNA fidelity whereas most metabolic pathways of intermediary metabolism were under expressed. Comparison of the dataset to a number of previously published microarray datasets revealed 1) a striking similarity between the fetal liver and that of the pancreas in both mice and humans, 2) a nucleated erythrocyte signature in the fetus and 3) under expression of most xenobiotic metabolism genes throughout development, with the exception of a number of transporters associated with either hematopoietic cells or cell proliferation in hepatocytes.</p> <p>Conclusions</p> <p>Overall, these findings reveal the complexity of gene expression changes during liver development and maturation, and provide a foundation to predict responses to chemical and drug exposure as a function of early life-stages.</p

A hepatitis C avidity test for determining recent and past infections in both plasma and dried blood spots

DBS testing has been used successfully to detect HCV antibody positive individuals. Determining how long someone has been infected is important for surveillance initiatives. Antibody avidity is a method that can be used to calculate recency of infection. A HCV avidity assay was evaluated for both plasma and DBS. Study design: To measure antibody avidity a commercial HCV ELISA was modified using 7 M urea. The plasma samples were split into: group 1 (recently infected N = 19), group 2 (chronic carrier N = 300) and group 3 (resolved infection N = 82). Mock DBS made from group 1 (N = 12), group 2 (N = 50), group 3 (N = 25) and two seroconverter panels were evaluated. 133 DBS taken from patients known to have a resolved infection or be a chronic carrier were also tested. The avidity assay cut-off was set at AI ≤ 30 for a recent infection. Using sequential samples the assay could detect a recent infection in the first 4–5 months from the point of infection. Most of the false positive results (AI < 30 among cases known not to have had recent infection) were detected among known resolved infections, in both the plasma and DBS; as a result, a testing algorithm has been designed incorporating both PCR and two dilution factors. The sensitivity and specificity of the assay on plasma was 100% and 99.3%, respectively, while DBS had 100% sensitivity and 98.3% specificity. The HCV avidity assay can be used to distinguish between chronic and recent infection using either plasma or DBS as the sample type

Subchronic Pulmonary Pathology, Iron Overload, and Transcriptional Activity after Libby Amphibole Exposure in Rat Models of Cardiovascular Disease

Background: Surface-available iron (Fe) is proposed to contribute to asbestos-induced toxicity through the production of reactive oxygen species

Performance of Near-Infrared High-Contrast Imaging Methods with JWST from Commissioning

The James Webb Space Telescope (JWST) will revolutionize the field of high-contrast imaging and enable both the direct detection of Saturn-mass planets and the characterization of substellar companions in the mid-infrared. While JWST will feature unprecedented sensitivity, angular resolution will be the key factor when competing with ground-based telescopes. Here, we aim to characterize the performance of several extreme angular resolution imaging techniques available with JWST in the 3-5 µm regime based on data taken during the instrument commissioning. Firstly, we introduce custom tools to simulate, reduce, and analyze JWST NIRCam and MIRI coronagraphy data and use these tools to extract companion detection limits from on-sky NIRCam round and bar mask coronagraphy observations. Secondly, we present on-sky JWST NIRISS aperture masking interferometry (AMI) and kernel phase imaging (KPI) observations from which we extract companion detection limits using the publicly available fouriever tool. Scaled to a total integration time of one hour and a target of the brightness of AB Dor (W1 ≈ 4.4 mag, W2 ≈ 3.9 mag), we find that NIRISS AMI and KPI reach contrasts of ∼ 7-8 mag at ∼ 70 mas and ∼ 9 mag at ∼ 200 mas. Beyond ∼ 250 mas, NIRCam coronagraphy reaches deeper contrasts of ∼ 13 mag at ∼ 500 mas and ∼ 15 mag at ∼ 2 arcsec. While the bar mask performs ∼ 1 mag better than the round mask at small angular separations ≲ 0.75 arcsec, it is the other way around at large angular separations ≳ 1.5 arcsec. Moreover, the round mask gives access to the full 360 deg field-of-view which is beneficial for the search of new companions. We conclude that already during the instrument commissioning, JWST high-contrast imaging in the L- and M-bands performs close to its predicted limits and is a factor of ∼ 10 times better at large separations than the best ground-based instruments operating at similar wavelengths despite its \u3e 2 times smaller collecting area

Single hepatocytes show persistence and transcriptional inactivity of hepatitis B

© 2020, Balagopal et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License.There is no cure for the more than 270 million people chronically infected with HBV. Nucleos(t)ide analogs (NUCs), the mainstay of anti-HBV treatment, block HBV reverse transcription. NUCs do not eliminate the intranuclear covalently closed circular DNA (cccDNA), from which viral RNAs, including pregenomic RNA (pgRNA), are transcribed. A key gap in designing a cure is understanding how NUCs affect HBV replication and transcription because serum markers yield an incomplete view of intrahepatic HBV. We applied single-cell laser capture microdissection and droplet digital PCR to paired liver biopsies collected from 5 HBV/HIV-coinfected persons who took NUCs over 2-4 years. From biopsy 1 to 2, proportions of HBV-infected hepatocytes declined with adherence to NUC treatment (P < 0.05); we extrapolated that eradication of HBV will take over 10 decades with NUCs in these participants. In individual hepatocytes, pgRNA levels diminished 28- to 73-fold during NUC treatment, corresponding with decreased tissue HBV core antigen staining (P < 0.01). In 4 out of 5 participants, hepatocytes with cccDNA but undetectable pgRNA (transcriptionally inactive) were present, and these were enriched in 3 participants during NUC treatment. Further work to unravel mechanisms of cccDNA transcriptional inactivation may lead to therapies that can achieve this in all hepatocytes, resulting in a functional cure.info:eu-repo/semantics/publishedVersio

Improved Orbital Constraints and Hα\alpha Photometric Monitoring of the Directly Imaged Protoplanet Analog HD 142527 B

Companions embedded in the cavities of transitional circumstellar disks have been observed to exhibit excess luminosity at H$\alpha$, an indication that they are actively accreting. We report 5 years (2013-2018) of monitoring of the position and H$\alpha$ excess luminosity of the embedded, accreting low-mass stellar companion HD 142527 B from the MagAO/VisAO instrument. We use pyklip, a python implementation of the Karhounen-Loeve Image Processing algorithm, to detect the companion. Using pyklip forward modeling, we constrain the relative astrometry to $1-2 \mathrm{mas}$ precision and achieve sufficient photometric precision ($\pm0.2 \mathrm{mag}, 3\%$ error) to detect changes in the H$\alpha$ contrast of the companion over time. In order to accurately determine the relative astrometry of the companion, we conduct an astrometric calibration of the MagAO/VisAO camera against 20 years of Keck/NIRC2 images of the Trapezium cluster. We demonstrate agreement of our VisAO astrometry with other published positions for HD 142527 B, and use orbitize! to generate a posterior distribution of orbits fit to the relative astrometry of HD 142527 B. Our data suggest that the companion is close to periastron passage, on an orbit significantly misinclined with respect to both the wide circumbinary disk and the recently observed inner disk encircling HD 142527 A. We translate observed H-alpha contrasts for HD 142527 B into mass accretion rate estimates on the order of $4-9\times10^{-10} \mathrm{M_\odot}\mathrm{yr}^{-1}$. Photometric variation in the H-alpha excess of the companion suggests that the accretion rate onto the companion is variable. This work represents a significant step towards observing accretion-driven variability onto protoplanets, such as PDS 70 b\&c.Comment: Accepted to the Astronomical Journal. 32 pages, 16 figures, 8 tables, 4 appendice