7,405 research outputs found

    Singing from the Grave: DNA from a 180 Year Old Type Specimen Confirms the Identity of Chrysoperla carnea (Stephens)

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    Copyright: © 2015 Price et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The attached file is the published version of the article

    Cyfip1 Haploinsufficiency Does Not Alter GABAA Receptor δ-Subunit Expression and Tonic Inhibition in Dentate Gyrus PV+ Interneurons and Granule Cells

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    Copy number variation (CNV) at chromosomal region 15q11.2 is linked to increased risk of neurodevelopmental disorders including autism and schizophrenia. A significant gene at this locus is cytoplasmic fragile X mental retardation protein (FMRP) interacting protein 1 (CYFIP1). CYFIP1 protein interacts with FMRP, whose monogenic absence causes fragile X syndrome (FXS). Fmrp knock-out has been shown to reduce tonic GABAergic inhibition by interacting with the δ-subunit of the GABAA receptor (GABAAR). Using in situ hybridization (ISH), qPCR, Western blotting techniques, and patch clamp electrophysiology in brain slices from a Cyfip1 haploinsufficient mouse, we examined δ-subunit mediated tonic inhibition in the dentate gyrus (DG). In wild-type (WT) mice, DG granule cells (DGGCs) responded to the δ-subunit-selective agonist THIP with significantly increased tonic currents. In heterozygous mice, no significant difference was observed in THIP-evoked currents in DGGCs. Phasic GABAergic inhibition in DGGC was also unaltered with no difference in properties of spontaneous IPSCs (sIPSCs). Additionally, we demonstrate that DG granule cell layer (GCL) parvalbumin-positive interneurons (PV+-INs) have functional δ-subunit-mediated tonic GABAergic currents which, unlike DGGC, are also modulated by the α1-selective drug zolpidem. Similar to DGGC, both IPSCs and THIP-evoked currents in PV+-INs were not different between Cyfip1 heterozygous and WT mice. Supporting our electrophysiological data, we found no significant change in hippocampal δ-subunit mRNA expression or protein level and no change in α1/α4-subunit mRNA expression. Thus, Cyfip1 haploinsufficiency, mimicking human 15q11.2 microdeletion syndrome, does not alter hippocampal phasic or tonic GABAergic inhibition, substantially differing from the Fmrp knock-out mouse model

    Novel Host-Related Virulence Factors Are Encoded by Squirrelpox Virus, the Main Causative Agent of Epidemic Disease in Red Squirrels in the UK

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    Squirrelpox virus (SQPV) shows little evidence for morbidity or mortality in North American grey squirrels (Sciurus carolinensis), in which the virus is endemic. However, more recently the virus has emerged to cause epidemics with high mortality in Eurasian red squirrels (S. vulgaris) in Great Britain, which are now threatened. Here we report the genome sequence of SQPV. Comparison with other Poxviridae revealed a core set of poxvirus genes, the phylogeny of which showed SQPV to be in a new Chordopoxvirus subfamily between the Molluscipoxviruses and Parapoxviruses. A number of SQPV genes were related to virulence, including three major histocomaptibility class I homologs, and one CD47 homolog. In addition, a novel potential virulence factor showing homology to mammalian oligoadenylate synthetase (OAS) was identified. This family of proteins normally causes activation of an endoribonuclease (RNaseL) within infected cells. The putative function of this novel SQPV protein was predicted in silico

    The Effect of Antidepressants on the Course of Inflammatory Bowel Disease

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    Background and Aims. Mood may have an important role in the natural history of inflammatory bowel disease (IBD). However, the impact of antidepressant use on prognosis is unknown. We aimed to address this in a longitudinal study in a referral population. Methods. We collected demographic data, clinical disease activity and mood using validated questionnaires, and antidepressant use at baseline. Longitudinal disease activity was defined by disease flare or need for glucocorticosteroids, escalation of medical therapy, hospitalisation, or intestinal resection. We compared rates of these over a minimum period of 2 years according to antidepressant use at baseline. Results. In total, 331 patients provided complete data, of whom 54 (15.8%) were taking an antidepressant at study entry. Older age, female gender, and abnormal mood scores were associated with antidepressant use. During longitudinal follow-up, there was a trend towards lower rates of any of the four endpoints of IBD activity of interest in patients with abnormal anxiety scores at baseline and who were receiving an antidepressant (42.3% versus 64.6%, P = 0.05). Based on univariate Cox regression analysis, there was a trend towards lower rates of escalation of medical therapy among patients receiving antidepressants at baseline (hazard ratio (HR) = 0.59; 95% confidence interval (CI) 0.35-1.00, P = 0.05). None of the differences observed persisted after multivariate Cox regression. Conclusions. Antidepressants may have some beneficial effects on the natural history of IBD, but larger studies with longer follow-up are required. Whether these effects are limited to patients with abnormal mood remains uncertain

    mmView: a web-based viewer of the mmCIF format

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    <p>Abstract</p> <p>Background</p> <p>Structural biomolecular data are commonly stored in the PDB format. The PDB format is widely supported by software vendors because of its simplicity and readability. However, the PDB format cannot fully address many informatics challenges related to the growing amount of structural data. To overcome the limitations of the PDB format, a new textual format mmCIF was released in June 1997 in its version 1.0. mmCIF provides extra information which has the advantage of being in a computer readable form. However, this advantage becomes a disadvantage if a human must read and understand the stored data. While software tools exist to help to prepare mmCIF files, the number of available systems simplifying the comprehension and interpretation of the mmCIF files is limited.</p> <p>Findings</p> <p>In this paper we present mmView - a cross-platform web-based application that allows to explore comfortably the structural data of biomacromolecules stored in the mmCIF format. The mmCIF categories can be easily browsed in a tree-like structure, and the corresponding data are presented in a well arranged tabular form. The application also allows to display and investigate biomolecular structures via an integrated Java application Jmol.</p> <p>Conclusions</p> <p>The mmView software system is primarily intended for educational purposes, but it can also serve as a useful research tool. The mmView application is offered in two flavors: as an open-source stand-alone application (available from <url>http://sourceforge.net/projects/mmview</url>) that can be installed on the user's computer, and as a publicly available web server.</p

    Longitudinal variation in O6-alkylguanine DNA-alkyltransferase activity in the human colon and rectum

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    In a systematic study of O6-alkylguanine DNA-alkyltransferase activity in the human colon and rectum, tumours were found to occur in regions of low activity. These results are consistent with the hypothesis that O6-alkylguanine DNA-alkyltransferase levels and alkylating agent exposure may be important determinants of large bowel tumorigenesis

    The chemistry of protoplanetary fragments formed via gravitational instabilities

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    In this paper, we model the chemical evolution of a 0.25 M_{\odot} protoplanetary disc surrounding a 1 M_{\odot} star that undergoes fragmentation due to self-gravity. We use Smoothed Particle Hydrodynamics including a radiative transfer scheme, along with time-dependent chemical evolution code to follow the composition of the disc and resulting fragments over approximately 4000 yrs. Initially, four quasi-stable fragments are formed, of which two are eventually disrupted by tidal torques in the disc. From the results of our chemical modelling, we identify species that are abundant in the fragments (e.g. H2_{\rm 2}O, H2_{\rm 2}S, HNO, N2_{\rm 2}, NH3_{\rm 3}, OCS, SO), species that are abundant in the spiral shocks within the disc (e.g. CO, CH4_{\rm 4}, CN, CS, H2_{\rm 2}CO), and species which are abundant in the circumfragmentary material (e.g. HCO+^{\rm +}). Our models suggest that in some fragments it is plausible for grains to sediment to the core before releasing their volatiles into the planetary envelope, leading to changes in, e.g., the C/O ratio of the gas and ice components. We would therefore predict that the atmospheric composition of planets generated by gravitational instability should not necessarily follow the bulk chemical composition of the local disc material
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