1,244 research outputs found

    Dynamic glycosylation of the transcription factor CREB: A potential role in gene regulation

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    We report that CREB (cyclic AMP-responsive element-binding protein), a transcription factor essential for long-term memory, is O-GlcNAc glycosylated in the mammalian brain. Glycosylation occurs at two sites within the Q2 domain and disrupts the interaction between CREB and TAF_(II)130, thereby repressing the transcriptional activity of CREB in vitro. These findings have important implications for the role of O-GlcNAc glycosylation in gene regulation, and they provide a link between O-GlcNAc and information storage processes in the brain

    Seroconversion for cytomegalovirus infection in a cohort of pregnant women in QuĂ©bec, 2010–2013

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    Cytomegalovirus (CMV) is the leading cause of congenital infection and non-genetic sensorineural hearing loss in children. There are no recent data on the incidence of CMV infection during pregnancy in Canada. This present study was undertaken to determine the seroprevalence of CMV IgG antibodies and the rate of seroconversion in a cohort of pregnant women in the province of QuĂ©bec, Canada. We used serum samples and questionnaire data collected as part of the 3D Pregnancy and Birth Cohort Study (2010–2013) conducted in QuĂ©bec, Canada. CMV IgG antibodies were determined in serum samples collected at the first and third trimesters. Associations between independent variables and seroprevalence were assessed using logistic regression, and associations with seroconversions, by Poisson regression. Of 1938 pregnant women tested, 40·4% were seropositive for CMV at baseline. Previous CMV infection was associated with: working as a daycare educator, lower education, lower income, having had children, first language other than French or English, and being born outside Canada or the United States. Of the 1122 initially seronegative women, 24 (2·1%) seroconverted between their first and third trimesters. The seroconversion rate was 1·4 [95% confidence interval (CI) 0·9–2·1]/ 10 000 person-days at risk or 3·9 (95% CI 2·5–5·9)/100 pregnancies (assuming a 280-day gestation). The high proportion of pregnant women susceptible to CMV infection (nearly 60%) and the subsequent rate of seroconversion are of concern

    Targeted expression profiling reveals distinct stages of early canine fibroblast reprogramming are regulated by 2-oxoglutarate hydroxylases

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    Background: Ectopic expression of a defined set of transcription factors allows the reprogramming of mammalian somatic cells to pluripotency. Despite continuous progress in primate and rodent reprogramming, limited attention has been paid to cell reprogramming in domestic and companion species. Previous studies attempting to reprogram canine cells have mostly assessed a small number of presumptive canine induced pluripotent stem cell (iPSC) lines for generic pluripotency attributes. However, why canine cell reprogramming remains extremely inefficient is poorly understood. Methods: To better characterize the initial steps of pluripotency induction in canine somatic cells, we optimized an experimental system where canine fetal fibroblasts (cFFs) are transduced with the Yamanaka reprogramming factors by Sendai virus vectors. We use quantitative PCR arrays to measure the expression of 80 target genes at various stages of canine cell reprogramming. We ask how cFF reprogramming is influenced by small molecules affecting the epigenomic modification 5-hydroxymethylcytosine, specifically L-ascorbic acid and retinoic acid (AA/RA). Results: We found that the expression and catalytic output of a class of 2-oxoglutarate-dependent (2-OG) hydroxylases, known as ten-eleven translocation (TET) enzymes, can be modulated in canine cells treated with AA/RA. We further show that AA/RA treatment induces TET1 expression and facilitates early canine reprogramming, evidenced by upregulation of epithelial and pluripotency markers. Using a chemical inhibitor of 2-OG hydroxylases, we demonstrate that 2-OG hydroxylase activity regulates the expression of a subset of genes involved in mesenchymal-to-epithelial transition (MET) and pluripotency in early canine reprogramming. We identify a set of transcription factors depleted in maturing reprogramming intermediates compared to pluripotent canine embryonic stem cells. Conclusions: Our findings highlight 2-OG hydroxylases have evolutionarily conserved and divergent functions regulating the early reprogramming of canine somatic cells and show reprogramming conditions can be rationally optimized for the generation of maturing canine iPSC

    Estimates of metabolic rate and major constituents of metabolic demand in fishes under field conditions: Methods, proxies, and new perspectives

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    Metabolic costs are central to individual energy budgets, making estimates of metabolic rate vital to understanding how an organism interacts with its environment as well as the role of species in their ecosystem. Despite the ecological and commercial importance of fishes, there are currently no widely adopted means of measuring field metabolic rate in fishes. The lack of recognized methods is in part due to the logistical difficulties of measuring metabolic rates in free swimming fishes. However, further development and refinement of techniques applicable for field-based studies on free swimming animals would greatly enhance the capacity to study fish under environmentally relevant conditions. In an effort to foster discussion in this area, from field ecologists to biochemists alike, we review aspects of energy metabolism and give details on approaches that have been used to estimate energetic parameters in fishes. In some cases, the techniques have been applied to field conditions; while in others, the methods have been primarily used on laboratory held fishes but should be applicable, with validation, to fishes in their natural environment. Limitations, experimental considerations and caveats of these measurements and the study of metabolism in wild fishes in general are also discussed. Potential novel approaches to FMR estimates are also presented for consideration. The innovation of methods for measuring field metabolic rate in free-ranging wild fish would revolutionize the study of physiological ecology

    Photoionization spectroscopy of CH3C3N in the vacuum-ultraviolet range

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    International audienceUsing vacuum-ultraviolet (VUV) synchrotron radiation, threshold and dissociative photoionization of cyanopropyne (CH3C3N) in the gas phase have been studied from 86 000 cm−1 up to 180 000 cm−1 by recording Threshold-PhotoElectron Spectrum (TPES) and PhotoIon Yield (PIY). Ionization energies of the four lowest electronic states X̃+2E,Ã+2A1,B̃+2E and C̃+ of CH3C3N+ are derived from the TPES with a better accuracy than previously reported. The adiabatic ionization potential of CH3C3N is measured as 86872±20 cm−1. A description of the vibrational structure of these states is proposed leading to the first determination of the vibrational frequencies for most modes. The vibrational assignments of the X̃+ state are supported by density functional theory calculations. In addition, dissociative photoionization spectra have been recorded for several cationic fragments in the range 12–15.5 eV (96 790–125 000 cm−1) and they bring new information on the photophysics of CH3C3N+. Threshold energies for the cationic dissociative channels leading to CH2C3N+, CHC3N+, HC3H+, HCNH+ and CH3+ have been measured for the first time and are compared with quantum chemical calculations

    The complete submillimetre spectrum of NGC 891

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    Submillimetre maps of NGC 891 have been obtained with the PRONAOS balloon-borne telescope and with the ISOPHOT instrument on board the ISO satellite. In this article, we also gather data from IRAS and SCUBA to present the complete submillimetre spectrum of this nearby edge-on spiral galaxy. We derive submillimetre emission profiles along the major axis. The modified blackbody fits, assuming a single dust component, lead to temperatures of 19-24 K toward the centre and 18-20 K toward the edges, with possible variations of the dust spectral index from 1.4 to 2. The two-component fits lead to a warm component temperature of 29 K all along the galaxy with a cold component at 16 K. The interstellar medium masses derived by these two methods are quite different: 4.6 x 10^9 Mo in the case of the one-component model and 12 x 10^9 Mo in the case of the two-component one. This two-component fit indicates that the cold dust to warm dust ratio is 20 to 40, the highest values being in the wings of this galaxy. Comparing to dust mass estimates, both estimations of the ISM mass are consistent with a gas to dust mass ratio of 240, which is close to the Milky Way value. Our results illustrate the importance of accurate submillimetre spectra to derive masses of the interstellar medium in galaxies.Comment: 5 pages, 2 figures, accepted May 2003 in the MNRA

    Instrumental and Analytic Methods for Bolometric Polarimetry

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    We discuss instrumental and analytic methods that have been developed for the first generation of bolometric cosmic microwave background (CMB) polarimeters. The design, characterization, and analysis of data obtained using Polarization Sensitive Bolometers (PSBs) are described in detail. This is followed by a brief study of the effect of various polarization modulation techniques on the recovery of sky polarization from scanning polarimeter data. Having been successfully implemented on the sub-orbital Boomerang experiment, PSBs are currently operational in two terrestrial CMB polarization experiments (QUaD and the Robinson Telescope). We investigate two approaches to the analysis of data from these experiments, using realistic simulations of time ordered data to illustrate the impact of instrumental effects on the fidelity of the recovered polarization signal. We find that the analysis of difference time streams takes full advantage of the high degree of common mode rejection afforded by the PSB design. In addition to the observational efforts currently underway, this discussion is directly applicable to the PSBs that constitute the polarized capability of the Planck HFI instrument.Comment: 23 pages, 11 figures. for submission to A&

    Submillimeter mapping and analysis of cold dust condensations in the Orion M42 star forming complex

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    We present here the continuum submillimeter maps of the molecular cloud around the M42 Nebula in the Orion region. These have been obtained in four wavelength bands (200, 260, 360 and 580 microns) with the ProNaOS two meter balloon-borne telescope. The area covered is 7 parsecs wide (50 arcmin at a distance of 470 pc) with a spatial resolution of about 0.4 parsec. Thanks to the high sensitivity to faint surface brightness gradients, we have found several cold condensations with temperatures ranging from 12 to 17 K, within 3 parsecs of the dense ridge. The statistical analysis of the temperature and spectral index spatial distribution shows an evidence of an inverse correlation between these two parameters. Being invisible in the IRAS 100 micron survey, some cold clouds are likely to be the seeds for future star formation activity going on in the complex. We estimate their masses and we show that two of them have masses higher than their Jeans masses, and may be gravitationally unstable.Comment: 4 figures, The Astrophysical Journal, Main Journal, in pres

    A Chemoenzymatic Approach toward the Rapid and Sensitive Detection of O-GlcNAc Posttranslational Modifications

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    We report a new chemoenzymatic strategy for the rapid and sensitive detection of O-GlcNAc posttranslational modifications. The approach exploits the ability of an engineered mutant of ÎČ-1,4-galactosyltransferase to selectively transfer an unnatural ketone functionality onto O-GlcNAc glycosylated proteins. Once transferred, the ketone moiety serves as a versatile handle for the attachment of biotin, thereby enabling chemiluminescent detection of the modified protein. Importantly, this approach permits the rapid visualization of proteins that are at the limits of detection using traditional methods. Moreover, it bypasses the need for radioactive precursors and captures the glycosylated species without perturbing metabolic pathways. We anticipate that this general chemoenzymatic strategy will have broad application to the study of posttranslational modifications

    Planck pre-launch status: HFI beam expectations from the optical optimisation of the focal plane

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    Planck is a European Space Agency (ESA) satellite, launched in May 2009, which will map the cosmic microwave background anisotropies in intensity and polarisation with unprecedented detail and sensitivity. It will also provide full-sky maps of astrophysical foregrounds. An accurate knowledge of the telescope beam patterns is an essential element for a correct analysis of the acquired astrophysical data. We present a detailed description of the optical design of the High Frequency Instrument (HFI) together with some of the optical performances measured during the calibration campaigns. We report on the evolution of the knowledge of the pre-launch HFI beam patterns when coupled to ideal telescope elements, and on their significance for the HFI data analysis procedure
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