419 research outputs found
Reconstructing ‘the Alcoholic’: Recovering from Alcohol Addiction and the Stigma this Entails
Public perception of alcohol addiction is frequently negative, whilst an important part of recovery is the construction of a positive sense of self. In order to explore how this might be achieved, we investigated how those who self-identify as in recovery from alcohol problems view themselves and their difficulties with alcohol and how they make sense of others’ responses to their addiction. Semi-structured interviews with six individuals who had been in recovery between 5 and 35 years and in contact with Alcoholics Anonymous were analysed using Interpretative Phenomenological Analysis. The participants were acutely aware of stigmatising images of ‘alcoholics’ and described having struggled with a considerable dilemma in accepting this identity themselves. However, to some extent they were able to resist stigma by conceiving of an ‘aware alcoholic self’ which was divorced from their previously unaware self and formed the basis for a new more knowing and valued identity
Insights into the Genomics of Clownfish Adaptive Radiation: Genetic Basis of the Mutualism with Sea Anemones.
Clownfishes are an iconic group of coral reef fishes, especially known for their mutualism with sea anemones. This mutualism is particularly interesting as it likely acted as the key innovation that triggered clownfish adaptive radiation. Indeed, after the acquisition of the mutualism, clownfishes diversified into multiple ecological niches linked with host and habitat use. However, despite the importance of this mutualism, the genetic mechanisms allowing clownfishes to interact with sea anemones are still unclear. Here, we used a comparative genomics and molecular evolutionary analyses to investigate the genetic basis of clownfish mutualism with sea anemones. We assembled and annotated the genome of nine clownfish species and one closely related outgroup. Orthologous genes inferred between these species and additional publicly available teleost genomes resulted in almost 16,000 genes that were tested for positively selected substitutions potentially involved in the adaptation of clownfishes to live in sea anemones. We identified 17 genes with a signal of positive selection at the origin of clownfish radiation. Two of them (Versican core protein and Protein O-GlcNAse) show particularly interesting functions associated with N-acetylated sugars, which are known to be involved in sea anemone discharge of toxins. This study provides the first insights into the genetic mechanisms of clownfish mutualism with sea anemones. Indeed, we identified the first candidate genes likely to be associated with clownfish protection form sea anemones, and thus the evolution of their mutualism. Additionally, the genomic resources acquired represent a valuable resource for further investigation of the genomic basis of clownfish adaptive radiation
The INTEGRAL/IBIS Scientific Data Analysis
The gamma-ray astronomical observatory INTEGRAL, succesfully launched on 17th
October 2002, carries two large gamma-ray telescopes. One of them is the
coded-mask imaging gamma-ray telescope onboard the INTEGRAL satellite (IBIS)
which provides high-resolution (~ 12') sky images of 29deg x 29deg in the
energy range from 15 keV to 10 MeV with typical on-axis sensitivity of ~ 1
mCrab at 100 keV (3 sigma, 10E6 s exposure). We report here the general
description of the IBIS coded-mask imaging system and of the standard IBIS
science data analysis procedures. These procedures reconstruct, clean and
combine IBIS sky images providing at the same time detection, identification
and preliminary analysis of point-like sources present in the field. Spectral
extraction has also been implemented and is based on simultaneous fitting of
source and background shadowgram models to detector images. The procedures are
illustrated using some of the IBIS data collected during the inflight
calibrations and present performance is discussed. The analysis programs
described here have been integrated as instrument specific software in the
Integral Science Data Center (ISDC) analysis software packages currently used
for the Quick Look, Standard and Off-line Scientific Analysis.Comment: 7 pages, 13 figures (6 color), accepted for publication in A&A Lett
(INTEGRAL special issue). Full resulution color figures can be found in the
printed version of the paper (see
http://www.edpsciences.org/articles/aa/abs/2003/43/contents/contents.html
Asymmetric dimerization in a transcription factor superfamily is promoted by allosteric interactions with DNA
Transcription factors, such as nuclear receptors achieve precise transcriptional regulation by means of a tight and reciprocal communication with DNA, where cooperativity gained by receptor dimerization is added to binding site sequence specificity to expand the range of DNA target gene sequences. To unravel the evolutionary steps in the emergence of DNA selection by steroid receptors (SRs) from monomeric to dimeric palindromic binding sites, we carried out crystallographic, biophysical and phylogenetic studies, focusing on the estrogen-related receptors (ERRs, NR3B) that represent closest relatives of SRs. Our results, showing the structure of the ERR DNA-binding domain bound to a palindromic response element (RE), unveil the molecular mechanisms of ERR dimerization which are imprinted in the protein itself with DNA acting as an allosteric driver by allowing the formation of a novel extended asymmetric dimerization region (KR-box). Phylogenetic analyses suggest that this dimerization asymmetry is an ancestral feature necessary for establishing a strong overall dimerization interface, which was progressively modified in other SRs in the course of evolution.journal articl
Transiting exoplanets from the CoRoT space mission VIII. CoRoT-7b: the first Super-Earth with measured radius
We report the discovery of very shallow (DF/F = 3.4 10-4), periodic dips in
the light curve of an active V = 11.7 G9V star observed by the CoRoT satellite,
which we interpret as due to the presence of a transiting companion. We
describe the 3-colour CoRoT data and complementary ground-based observations
that support the planetary nature of the companion. Methods. We use CoRoT color
information, good angular resolution ground-based photometric observations in-
and out- of transit, adaptive optics imaging, near-infrared spectroscopy and
preliminary results from Radial Velocity measurements, to test the diluted
eclipsing binary scenarios. The parameters of the host star are derived from
optical spectra, which were then combined with the CoRoT light curve to derive
parameters of the companion. We examine carefully all conceivable cases of
false positives, and all tests performed support the planetary hypothesis.
Blends with separation larger than 0.40 arcsec or triple systems are almost
excluded with a 8 10-4 risk left. We conclude that, as far as we have been
exhaustive, we have discovered a planetary companion, named CoRoT-7b, for which
we derive a period of 0.853 59 +/- 3 10-5 day and a radius of Rp = 1.68 +/-
0.09 REarth. Analysis of preliminary radial velocity data yields an upper limit
of 21 MEarth for the companion mass, supporting the finding.
CoRoT-7b is very likely the first Super-Earth with a measured radius.Comment: Accepted in Astronomy and Astrophysics; typos and language
corrections; version sent to the printer w few upgrade
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SEIS: Insight's Seismic Experiment for Internal Structure of Mars.
By the end of 2018, 42 years after the landing of the two Viking seismometers on Mars, InSight will deploy onto Mars' surface the SEIS (Seismic Experiment for Internal Structure) instrument; a six-axes seismometer equipped with both a long-period three-axes Very Broad Band (VBB) instrument and a three-axes short-period (SP) instrument. These six sensors will cover a broad range of the seismic bandwidth, from 0.01 Hz to 50 Hz, with possible extension to longer periods. Data will be transmitted in the form of three continuous VBB components at 2 sample per second (sps), an estimation of the short period energy content from the SP at 1 sps and a continuous compound VBB/SP vertical axis at 10 sps. The continuous streams will be augmented by requested event data with sample rates from 20 to 100 sps. SEIS will improve upon the existing resolution of Viking's Mars seismic monitoring by a factor of ∼ 2500 at 1 Hz and ∼ 200 000 at 0.1 Hz. An additional major improvement is that, contrary to Viking, the seismometers will be deployed via a robotic arm directly onto Mars' surface and will be protected against temperature and wind by highly efficient thermal and wind shielding. Based on existing knowledge of Mars, it is reasonable to infer a moment magnitude detection threshold of M w ∼ 3 at 40 ∘ epicentral distance and a potential to detect several tens of quakes and about five impacts per year. In this paper, we first describe the science goals of the experiment and the rationale used to define its requirements. We then provide a detailed description of the hardware, from the sensors to the deployment system and associated performance, including transfer functions of the seismic sensors and temperature sensors. We conclude by describing the experiment ground segment, including data processing services, outreach and education networks and provide a description of the format to be used for future data distribution.Electronic supplementary materialThe online version of this article (10.1007/s11214-018-0574-6) contains supplementary material, which is available to authorized users
IUPHAR-DB: new receptors and tools for easy searching and visualization of pharmacological data
The IUPHAR database is an established online reference resource for several important classes of human drug targets and related proteins. As well as providing recommended nomenclature, the database integrates information on the chemical, genetic, functional and pathophysiological properties of receptors and ion channels, curated and peer-reviewed from the biomedical literature by a network of experts. The database now includes information on 616 gene products from four superfamilies in human and rodent model organisms: G protein-coupled receptors, voltage- and ligand-gated ion channels and, in a recent update, 49 nuclear hormone receptors (NHRs). New data types for NHRs include details on co-regulators, DNA binding motifs, target genes and 3D structures. Other recent developments include curation of the chemical structures of approximately 2000 ligand molecules, providing electronic descriptors, identifiers, link-outs and calculated molecular properties, all available via enhanced ligand pages. The interface now provides intelligent tools for the visualization and exploration of ligand structure-activity relationships and the structural diversity of compounds active at each target. The database is freely available at http://www.iuphar-db.org
Drug and Cell Type-Specific Regulation of Genes with Different Classes of Estrogen Receptor β-Selective Agonists
Estrogens produce biological effects by interacting with two estrogen receptors, ERα and ERβ. Drugs that selectively target ERα or ERβ might be safer for conditions that have been traditionally treated with non-selective estrogens. Several synthetic and natural ERβ-selective compounds have been identified. One class of ERβ-selective agonists is represented by ERB-041 (WAY-202041) which binds to ERβ much greater than ERα. A second class of ERβ-selective agonists derived from plants include MF101, nyasol and liquiritigenin that bind similarly to both ERs, but only activate transcription with ERβ. Diarylpropionitrile represents a third class of ERβ-selective compounds because its selectivity is due to a combination of greater binding to ERβ and transcriptional activity. However, it is unclear if these three classes of ERβ-selective compounds produce similar biological activities. The goals of these studies were to determine the relative ERβ selectivity and pattern of gene expression of these three classes of ERβ-selective compounds compared to estradiol (E2), which is a non-selective ER agonist. U2OS cells stably transfected with ERα or ERβ were treated with E2 or the ERβ-selective compounds for 6 h. Microarray data demonstrated that ERB-041, MF101 and liquiritigenin were the most ERβ-selective agonists compared to estradiol, followed by nyasol and then diarylpropionitrile. FRET analysis showed that all compounds induced a similar conformation of ERβ, which is consistent with the finding that most genes regulated by the ERβ-selective compounds were similar to each other and E2. However, there were some classes of genes differentially regulated by the ERβ agonists and E2. Two ERβ-selective compounds, MF101 and liquiritigenin had cell type-specific effects as they regulated different genes in HeLa, Caco-2 and Ishikawa cell lines expressing ERβ. Our gene profiling studies demonstrate that while most of the genes were commonly regulated by ERβ-selective agonists and E2, there were some genes regulated that were distinct from each other and E2, suggesting that different ERβ-selective agonists might produce distinct biological and clinical effects
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