7,202 research outputs found

    Crucial cross-talk of interleukin-1β and progesterone in human choriocarcinoma

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    Copyright @ 2012 Spandidos Publications Ltd. This article can be accessed from the links below.This article has been made available through the Brunel Open Access Publishing Fund.Choriocarcinoma is a highly malignant epithelial tumour that is most often associated with hydatidiform mole and presents the most common emergency medical problem in the management of trophoblast disease. We hypothesise that the hormones/cytokines present within the tumour microenvironment play key roles in the development of choriocarcinoma. In this study we assessed the effects of interleukin-1β (IL-1β) on cell death in the presence or absence of the sex hormone progesterone using two choriocarcinoma cell lines (BeWo and JEG-3) as in vitro experimental models. Although IL-1β induced cell death in both cell lines, the effect was more pronounced in JEG-3 cells, where cell death reached 40% compared to 15% in BeWo cells. Cell death of JEG-3 cells in response to IL-1β was significantly decreased by co-treatment with 100 nM and 1000 nM progesterone and completely abolished at a progesterone concentration of 1000 nM. Progesterone was also able to induce phosphorylation of ERK1/2 in these cells. Pretreatment of JEG-3 cells with a specific MAPK inhibitor (UO126) inhibited progesterone's inhibitory effect on cell death. Collectively, these data provide evidence of cross-talk between progesterone and IL-1β in this aggressive and poorly understood tumour that involves activation of a MAPK pathway and involvement of numerous progesterone receptors.This research was funded by a National Institutes of Health Grant ESO12961. This article is made available through the Brunel Open Access Publishing Fund

    First Record of \u3ci\u3eOchlerotatus Japonicus\u3c/i\u3e (Diptera: Culicidae) in St. Joseph County, Indiana

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    A single female specimen of Ochlerotatus japonicus (Theobald)(formerly Aedes japonicus), the Asian bush mosquito, was captured in St. Joseph County, IN on 29 July 2004. This is the first report of that species in northern Indiana. Additional specimens were subsequently collected, indicating probable establishment throughout the county

    Characterisation and expression of β1-, β2- and β3-adrenergic receptors in the fathead minnow (Pimephales promelas)

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    This is the author’s version of a work that was accepted for publication in General and Comparative Endocrinology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published and may be accessed at the link below. Copyright © 2011 Elsevier B.V. All rights reserved.Complimentary DNAs for three beta-adrenergic receptors (βARs) were isolated and characterised in the fathead minnow. The encoded proteins of 402 (β(1)AR), 397 (β(2)AR) and 434 (β(3)AR) amino acids were homologous to other vertebrate βARs, and displayed the characteristic seven transmembrane helices of G Protein-coupled receptors. Motifs and amino acids shown to be important for ligand binding were conserved in the fathead minnow receptors. Quantitative RT-PCR revealed the expression of all receptors to be highest in the heart and lowest in the ovary. However, the β(1)AR was the predominant subtype in the heart (70%), and β(3)AR the predominant subtype in the ovary (53%). In the brain, β(1)AR expression was about 200-fold higher than that of β(2)- and β(3)AR, whereas in the liver, β(2)AR expression was about 20-fold and 100-fold higher than β(3)- and β(1)AR expression, respectively. Receptor gene expression was modulated by exposure to propranolol (0.001-1mg/L) for 21days, but not in a consistent, concentration-related manner. These results show that the fathead minnow has a beta-adrenergic receptor repertoire similar to that of mammals, with the molecular signatures required for ligand binding. An exogenous ligand, the beta-blocker propranolol, is able to alter the expression profile of these receptors, although the functional relevance of such changes remains to be determined. Characterisation of the molecular targets for beta-blockers in fish will aid informed environmental risk assessments of these drugs, which are known to be present in the aquatic environment.European Union as part of the ERAPharm project, Contract No. 511135 and NER

    Infrared Spectroscopy of the Diffuse Ionized Halo of NGC 891

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    We present infrared spectroscopy from the Spitzer Space Telescope at one disk position and two positions at a height of 1 kpc from the disk in the edge-on spiral NGC 891, with the primary goal of studying halo ionization. Our main result is that the [Ne III]/[Ne II] ratio, which provides a measure of the hardness of the ionizing spectrum free from the major problems plaguing optical line ratios, is enhanced in the extraplanar pointings relative to the disk pointing. Using a 2D Monte Carlo-based photo-ionization code which accounts for the effects of radiation field hardening, we find that this trend cannot be reproduced by any plausible photo-ionization model, and that a secondary source of ionization must therefore operate in gaseous halos. We also present the first spectroscopic detections of extraplanar PAH features in an external normal galaxy. If they are in an exponential layer, very rough emission scale-heights of 330-530 pc are implied for the various features. Extinction may be non-negligible in the midplane and reduce these scale-heights significantly. There is little significant variation in the relative emission from the various features between disk and extraplanar environment. Only the 17.4 micron feature is significantly enhanced in the extraplanar gas compared to the other features, possibly indicating a preference for larger PAHs in the halo.Comment: 35 pages in ApJ preprint format, 8 figures, accepted for publication in ApJ. Minor change to Introduction to give appropriate credit to earlier, related wor

    Strain Rate Sensitive Constitutive Equations

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    Stain rate sensitive constitutive equations using yield criterion which incorporates second and third invariants of stress deviato

    Analysis of rolling group therapy data using conditionally autoregressive priors

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    Group therapy is a central treatment modality for behavioral health disorders such as alcohol and other drug use (AOD) and depression. Group therapy is often delivered under a rolling (or open) admissions policy, where new clients are continuously enrolled into a group as space permits. Rolling admissions policies result in a complex correlation structure among client outcomes. Despite the ubiquity of rolling admissions in practice, little guidance on the analysis of such data is available. We discuss the limitations of previously proposed approaches in the context of a study that delivered group cognitive behavioral therapy for depression to clients in residential substance abuse treatment. We improve upon previous rolling group analytic approaches by fully modeling the interrelatedness of client depressive symptom scores using a hierarchical Bayesian model that assumes a conditionally autoregressive prior for session-level random effects. We demonstrate improved performance using our method for estimating the variance of model parameters and the enhanced ability to learn about the complex correlation structure among participants in rolling therapy groups. Our approach broadly applies to any group therapy setting where groups have changing client composition. It will lead to more efficient analyses of client-level data and improve the group therapy research community's ability to understand how the dynamics of rolling groups lead to client outcomes.Comment: Published in at http://dx.doi.org/10.1214/10-AOAS434 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

    Microwave-assisted synthesis of 3-aminobenzo[b]thiophene scaffolds for the preparation of kinase inhibitors

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    Microwave irradiation of 2-halobenzonitriles and methyl thioglycolate in the presence of triethylamine in DMSO at 130 °C provides rapid access to 3-aminobenzo[b]thiophenes in 58–96% yield. This transformation has been applied in the synthesis of the thieno[2,3-b]pyridine core motif of LIMK1 inhibitors, the benzo[4,5]thieno[3,2-e][1,4]diazepin-5(2H)-one scaffold of MK2 inhibitors and a benzo[4,5]thieno[3,2-d]pyrimidin-4-one inhibitor of the PIM kinases

    The factors associated with care-related quality of life of adults with intellectual disabilities in England: implications for policy and practice

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    Over the last three decades, quality of life (QoL) has been advocated as an indicator of social care outcomes for adults with intellectual disabilities. In England, the Adult Social Care Survey (ASCS) is conducted annually by local authorities to contribute to the evidence base of the care-related QoL of people receiving publicly-funded adult social care. This study explores relationships between QoL and non-care related factors to identify relationships that could inform social care policy and practice. Cross-sectional data collected from 13,642 adults who participated in the 2011 and 2012 ASCS were analysed using regression to explore the factors associated with QoL measured using the Adult Social Care Outcomes Toolkit (ASCOT). Self-rated health, rating of the suitability of home design and anxiety/depression were all found to be significantly associated with ASCOT. Other individual and survey completion factors were also found to have weak significant relationships with ASCOT. The models also indicate that there was an increase in overall ASCOT-QoL and in five of the eight ASCOT domains (Personal comfort and cleanliness, Safety, Social participation, Occupation and Dignity) between 2011 and 2012. These findings demonstrate the potential value of QoL data for informing policy for people with intellectual disabilities by identifying key factors associated with QoL, the characteristics of those at risk of lower QoL, and QoL domains that could be targeted for improvement over time. Future research should establish causal relationships and explore the risk-adjustment of scores to account for variation outside of the control of social care support
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