Functional conservation of a forebrain enhancer from the elephant shark (Callorhinchus milii) in zebrafish and mice

Background: The phylogenetic position of the elephant shark (Callorhinchus milii ) is particularly relevant to study the evolution of genes and gene regulation in vertebrates. Here we examine the evolution of Dlx homeobox gene regulation during vertebrate embryonic development with a particular focus on the forebrain. We first identified the elephant shark sequence orthologous to the URE2 cis -regulatory element of the mouse Dlx1/Dlx2 locus (herein named CmURE2). We then conducted a comparative study of the sequence and enhancer activity of CmURE2 with that of orthologous regulatory sequences from zebrafish and mouse. Results: The CmURE2 sequence shows a high percentage of identity with its mouse and zebrafish counterparts but is overall more similar to mouse URE2 (MmURE2) than to zebrafish URE2 (DrURE2). In transgenic zebrafish and mouse embryos, CmURE2 displayed enhancer activity in the forebrain that overlapped with that of DrURE2 and MmURE2. However, we detected notable differences in the activity of the three sequences in the diencephalon. Outside of the forebrain, CmURE2 shows enhancer activity in areas such as the pharyngeal arches and dorsal root ganglia where its' counterparts are also active. Conclusions: Our transgenic assays show that part of the URE2 enhancer activity is conserved throughout jawed vertebrates but also that new characteristics have evolved in the different groups. Our study demonstrates that the elephant shark is a useful outgroup to study the evolution of regulatory mechanisms in vertebrates and to address how changes in the sequence of cis -regulatory elements translate into changes in their regulatory activity

Very High Energy Gamma-ray spectral properties of Mrk 501 from CAT Cerenkov telescope observations in 1997

The BL Lac object Mrk 501 went into a very high state of activity during 1997, both in VHE gamma-rays and X-rays. We present here results from observations at energies above 250 GeV carried out between March and October 1997 with the CAT Cerenkov imaging Telescope. The average differential spectrum between 30 GeV and 13 TeV shows significant curvature and is well represented by phi_0 * E_TeV^{-(alpha + beta*log10(E_TeV))}, with: phi_0 = 5.19 +/- 0.13 {stat} +/- 0.12 {sys-MC} +1.66/-1.04 {sys-atm} * 10^-11 /cm^2/s/TeV alpha = 2.24 +/- 0.04 {stat} +/- 0.05 {sys} beta = 0.50 +/- 0.07 {stat} (negligible systematics). The TeV spectral energy distribution of Mrk 501 clearly peaks in the range 500 GeV-1 TeV. Investigation of spectral variations shows a significant hardness-intensity correlation with no measurable effect on the curvature. This can be described as an increase of the peak TeV emission energy with intensity. Simultaneous and quasi-simultaneous CAT VHE gamma-ray and BeppoSAX hard X-ray detections for the highest recorded flare on 16th April and for lower-activity states of the same period show correlated variability with a higher luminosity in X-rays than in gamma-rays. The observed spectral energy distribution and the correlated variability between X-rays and gamma-rays, both in amplitude and in hardening of spectra, favour a two-component emission scheme where the low and high energy components are attributed to synchrotron and inverse Compton (IC) radiation, respectively.Comment: Submitted to Astronomy and Astrophysics, 8 pages including 6 figures. Published with minor change

Spectrum and Variability of Mrk501 as observed by the CAT Imaging Telescope

The CAT Imaging Telescope has observed the BL Lac object Markarian 501 between March and August 1997. We report here on the variability over this time including several large flares. We present also preliminary spectra for all these data, for the low emission state, and for the largest flare.Comment: 4 pages, 4 figures, Late

Observation of the Crab Nebula Gamma-Ray Emission Above 220 Gev by the Cat Cherenkov Imaging Telescope

The CAT imaging telescope, recently built on the site of the former solar plant Themis (French Pyrenees), observed gamma-rays from the Crab nebula from October 1996 to March 1997. This steady source, often considered as the standard candle of very-high-energy gamma-ray astronomy, is used as a test-beam to probe the performances of the new telescope, particularly its energy threshold (220 GeV at 20 degrees zenith angle) and the stability of its response. Due to the fine-grain camera, an accurate analysis of the longitudinal profiles of shower images is performed, yielding the source position in two dimensions for each individual shower.Comment: 5 pages, 3 figures, Tex, contribution to 25th ICRC Durba

Detection of Vhe Gamma-Rays from MRK 501 with the Cat Imaging Telescope

The CAT imaging telescope on the site on the former solar plant Themis has been observing gamma-rays from Mrk501 above 220 GeV in March and April 1997. This source is shown to be highly variable and the light curve is presented. The detected gamma-ray rate for the most intense flare is in excess of 10 per minute.Comment: 5 pages, 4 figures, Tex, contribution to 25th ICRC Durba

The CAT Imaging Telescope for Very-High-Energy Gamma-Ray Astronomy

The CAT (Cherenkov Array at Themis) imaging telescope, equipped with a very-high-definition camera (546 fast phototubes with 0.12 degrees spacing surrounded by 54 larger tubes in two guard rings) started operation in Autumn 1996 on the site of the former solar plant Themis (France). Using the atmospheric Cherenkov technique, it detects and identifies very high energy gamma-rays in the range 250 GeV to a few tens of TeV. The instrument, which has detected three sources (Crab nebula, Mrk 421 and Mrk 501), is described in detail.Comment: 24 pages, 15 figures. submitted to Elsevier Preprin

Development and regeneration of the crushing dentition of skates (Rajidae)

Sharks and rays (elasmobranchs) have the remarkable capacity to continuously regenerate their teeth. The polyphyodont system is considered the ancestral condition of the gnathostome dentition. Despite this shared regenerative ability, sharks and rays exhibit dramatic interspecific variation in their tooth morphology. Ray (batoidea) teeth typically constitute crushing pads of flattened teeth, whereas shark teeth are pointed, multi-cuspid units. Although recent research has addressed the molecular development of the shark dentition, little is known about that of the ray. Furthermore, how dental diversity within the elasmobranch lineage is achieved remains unknown. Here, we examine dental development and regeneration in two Batoid species: the thornback skate (Raja clavata) and the little skate (Leucoraja erinacea). Using in situ hybridization and immunohistochemistry, we examine the expression of a core gnathostome dental gene set during early development of the skate dentition and compare it to development in the shark. Elasmobranch tooth development is highly conserved, with sox2 likely playing an important role in the initiation and regeneration of teeth. Alterations to conserved genes expressed in an enamel knot-like signalling centre may explain the morphological diversity of elasmobranch teeth, thereby enabling sharks and rays to occupy diverse dietary and ecological niches

Detection of the BL Lac object 1ES1426+428 in the Very High Energy gamma-ray band by the CAT Telescope from 1998-2000

The BL Lac Object 1ES 1426+428, at a red-shift of z=0.129, has been monitored by the CAT telescope from February 1998 to June 2000. The accumulation of 26 hours of observations shows a gamma-ray signal of 321 events above 250 GeV at 5.2 standard deviations, determined using data analysis cuts adapted to a weak, steep-spectrum source. The source emission has an average flux of Phi_diff(400 GeV) = 6.73 +/- 1.27stat +/- 1.45syst x 10^-11 /cm^-2/s/TeV, and a very steep spectrum, with a differential spectral index of gamma = -3.60 +/- 0.57 which can be refined to gamma = -3.66 +/- 0.41 using a higher flux data subset. If, as expected from its broad-band properties, the Very High Energy emission is hard at the source, these observations support a strong absorption effect of gamma-rays by the Intergalactic Infrared field.Comment: 4 pages, 3 figures, accepted for publication in A&A Letter

The CAT Imaging Telescope

The VHE gamma-ray imaging telescope CAT started taking data in October 1996. Located at the Themis solar site in southern France, it features a 17.7 m^2 Davies-Cotton mirror equipped with 600 PMT camera at the focal plane. The mechanics and optics, the PMTs and the electronics are presented. The performance, based on the first 7 months of operation, is described

Compliance and treatment satisfaction of post menopausal women treated for osteoporosis. Compliance with osteoporosis treatment

International audienceBackgroundAdherence to anti-osteoporosis treatments is poor, exposing treated women to increased fracture risk. Determinants of poor adherence are poorly understood. The study aims to determine physician- and patient- rated treatment compliance with osteoporosis treatments and to evaluate factors influencing compliance.MethodsThis was an observational, cross-sectional pharmacoepidemiological study with a randomly-selected sample of 420 GPs, 154 rheumatologists and 110 gynaecologists practicing in France. Investigators included post-menopausal women with a diagnosis of osteoporosis and a treatment initiated in the previous six months. Investigators completed a questionnaire on clinical features, treatments and medical history, and on patient compliance. Patients completed a questionnaire on sociodemographic features, lifestyle, attitudes and knowledge about osteoporosis, treatment compliance, treatment satisfaction and quality of life. Treatment compliance was evaluated with the Morisky Medication-taking Adherence Scale. Variables collected in the questionnaires were evaluated for association with compliance using multivariate logistic regression analysis.Results785 women were evaluated. Physicians considered 95.4% of the sample to be compliant, but only 65.5% of women considered themselves compliant. The correlation between patient and physician perceptions of compliance was low (κ: 0.11 [95% CI: 0.06 to 0.16]). Patient-rated compliance was highest for monthly bisphosphonates (79.7%) and lowest for hormone substitution therapy (50.0%). Six variables were associated with compliance: treatment administration frequency, perceptions of long-term treatment acceptability, perceptions of health consequences of osteoporosis, perceptions of knowledge about osteoporosis, exercise and mental quality of life.ConclusionCompliance to anti-osteoporosis treatments is poor. Reduction of dosing regimen frequency and patient education may be useful ways of improving compliance