9,287 research outputs found

    Functional consequence of a novel Y129C mutation in a patient with two contradictory melanocortin-2-receptor mutations

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    L F C and T-T C are supported by M R C Clinical Research Training Fellowships (grant numbers G0600408, G0700581) and L A M by the Wellcome Trust (grant number 076430/Z/05/7)

    Bioluminescence Resonance Energy Transfer Reveals the Adrenocorticotropin (ACTH)-Induced Conformational Change of the Activated ACTH Receptor Complex in Living Cells

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    Bioluminescence resonance energy transfer analysis is used to study the interaction between melanocortin 2 receptor (MC2R) accessory protein and the MC2R and provides evidence for protein kinase A-dependent conformational changes in the receptor complex following receptor activation. The melanocortin 2 receptor (MC2R) accessory protein (MRAP) is a small single-transmembrane domain protein that plays a pivotal role in the function of the MC2R. The pituitary hormone, ACTH, acts via this receptor complex to stimulate adrenal steroidogenesis. Using both coimmunoprecipitation and bioluminescence resonance energy transfer (BRET), we show that the MC2R is constitutively homodimerized in cells. Furthermore, consistent with previous data, we also show that MRAP exists as an antiparallel homodimer. ACTH enhanced the BRET signal between MC2R homodimers as well as MC2R-MRAP heterodimers. However, ACTH did not enhance the physical interaction between these dimers as determined by coimmunoprecipitation. Real-time BRET analysis of the MRAP-MC2R interaction revealed two distinct phases of the ACTH-dependent BRET increase, an initial complex series of changes occurring over the first 2 min and a later persistent increase in BRET signal. The slower ACTH-dependent phase was inhibited by the protein kinase A inhibitor KT5720, suggesting that signal transduction was a prerequisite for this later conformational change. The MRAP-MC2R BRET approach provides a unique tool with which to analyze the activation of this receptor

    On the AJ Conjecture for Knots

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    We confirm the AJ conjecture [Ga2] that relates the A-polynomial and the colored Jones polynomial for hyperbolic knots satisfying certain conditions. In particular, we show that the conjecture holds true for some classes of two-bridge knots and pretzel knots. This extends the result of the first author in [Le2], who established the AJ conjecture for a large class of two-bridge knots, including all twist knots. Along the way, we explicitly calculate the universal SL₂(C)-character ring of the knot group of the (−2, 3, 2n + 1)-pretzel knot, and show it is reduced for all integers n

    Nasica and Fides

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    The full-text of this article is not currently available in ORA, but you may be able to access the article via the publisher copy link on this record page. Citation: Clark, A. J. (2007). 'Nasica and Fides', Classical Quarterly 57(1), 125-131. [Available at http://journals.cambridge.org/action/displayJournal?jid=caq]

    Discovery of a single faint AGN in a large sample of z > 5 Lyman break galaxies

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    As part of a large spectroscopic survey of z > 5 Lyman break galaxies (LBGs), we have identified a single source which is clearly hosting an active galactic nucleus (AGN). Out of a sample of more than 50 spectroscopically confirmed R-band dropout galaxies at z∼ 5 and above, only J104048.6−115550.2 at z= 5.44 shows evidence for a high ionization potential emission line indicating the presence of a hard ionizing continuum from an AGN. Like most objects in our sample the rest-frame-UV spectrum shows the UV continuum breaking across a Lyα line. Uniquely within this sample of LBGs, emission from N V is also detected, a clear signature of AGN photoionization. The object is spatially resolved in Hubble Space Telescope (HST) imaging. This, and the comparatively high Lyα/N V flux ratio indicates that the majority of the Lyα (and the UV continuum longward of it) originates from stellar photoionization, a product of the ongoing starburst in the LBG. Even without the AGN emission, this object would have been photometrically selected and spectroscopically confirmed as a Lyman break in our survey. The measured optical flux (IAB= 26.1) is therefore an upper limit to that from the AGN and is of order 100 times fainter than the majority of known quasars at these redshifts. The detection of a single object in our survey volume is consistent with the best current models of high redshift AGN luminosity function, providing a substantial fraction of such AGN is found within luminous starbursting galaxies. We discuss the cosmological implications of this discovery

    Radio sources in the Chandra Galactic Bulge Survey

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    We discuss radio sources in the Chandra Galactic Bulge Survey region. By cross-matching the X-ray sources in this field with the NRAO VLA Sky Survey archival data, we find 12 candidate matches. We present a classification scheme for radio/X-ray matches in surveys taken in or near the Galactic plane, taking into account other multiwavelength data. We show that none of the matches found here is likely to be due to coronal activity from normal stars because the radio to X-ray flux ratios are systematically too high. We show that one of the source could be a radio pulsar, and that one could be a planetary nebula, but that the bulk of the sources are likely to be background active galactic nuclei (AGN), with many confirmed through a variety of approaches. Several of the AGN are bright enough in the near-infrared (and presumably in the optical) to use as probes of the interstellar medium in the inner Galaxy
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