1,410 research outputs found

    Brainstem Raphe Pallidus and the Adjacent Area Contain a Novel Action Site in the Melanocortin Circuitry Regulating Energy Balance

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    The central melanocortin system plays a critical role in the regulation of energy balance in rodents and humans. The melanocortin signals in both the hypothalamus and brainstem contribute to this regulation. However, how the melanocortin signals of the hypothalamus interact with those intrinsic to the brainstem in the regulation of energy balance is poorly understood. The brainstem raphe pallidus (RPa) and adjacent areas contain melanocortin 4 receptor (MC4-R)-bearing neurons and sympathetic premotor neurons regulating thermogenesis. Here we report that α-melanocyte-stimulating hormone (α-MSH)-immunoreactive (IR) fibers are in close apposition to MC4-R neurons in the RPa. Retrograde tracing studies revealed a unique direct projection from hypothalamic proopiomelanocortin (POMC) neurons to the RPa and adjacent areas of the brainstem in mice and rats. Furthermore, microinjection of the MC3/4-R agonist MTII into the RPa area dose-dependently stimulated oxygen consumption and inhibited feeding, whereas microinjection of the antagonist, SHU9119, enhanced feeding. These data suggest a novel pathway of hypothalamic POMC neuronal efferents to brainstem RPa area MC4-R neurons in the melanocortin circuitry that contribute to coordinate regulation of energy balance

    A Submillimetre Survey of the Hubble Deep Field: Unveiling Dust-Enshrouded Star Formation in the Early Universe

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    The advent of sensitive sub-mm array cameras now allows a proper census of dust-enshrouded massive star-formation in very distant galaxies, previously hidden activity to which even the deepest optical images are insensitive. We present the deepest sub-mm survey, taken with the SCUBA camera on the James Clerk Maxwell Telescope (JCMT) and centred on the Hubble Deep Field (HDF). The high source density on this image implies that the survey is confusion-limited below a flux density of 2 mJy. However within the central 80 arcsec radius independent analyses yield 5 reproducible sources with S(850um) > 2 mJy which simulations indicate can be ascribed to individual galaxies. These data lead to integral source counts which are completely inconsistent with a no evolution model, whilst the combined brightness of the 5 most secure sources in our map is sufficient to account for 30-50% of the previously unresolved sub-mm background, and statistically the entire background is resolved at about the 0.3 mJy level. Four of the five brightest sources appear to be associated with galaxies which lie in the redshift range 2 < z < 4. With the caveat that this is a small sample of sources detected in a small survey area, these submm data imply a star-formation density over this redshift range that is at least five times higher than that inferred from the rest-frame ultraviolet output of HDF galaxies.Comment: to appear in the proceedings of `The Birth of Galaxies', Xth Rencontres de Blois, 4 pages, 1 postscript figure, uses blois.sty (included

    Promoter Recognition by a Complex of Spx and the C-Terminal Domain of the RNA Polymerase α Subunit

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    Spx, an ArsC (arsenate reductase) family member, is a global transcriptional regulator of the microbial stress response and is highly conserved amongst Gram-positive bacteria. Bacillus subtilis Spx protein exerts positive and negative control of transcription through its interaction with the C-terminal domain of the RNA polymerase (RNAP) alpha subunit (alphaCTD). Spx activates trxA (thioredoxin) and trxB (thioredoxin reductase) in response to thiol stress, and bears an N-terminal C10XXC13 redox disulfide center that is oxidized in active Spx.The structure of mutant Spx(C10S) showed a change in the conformation of helix alpha4. Amino acid substitutions R60E and K62E within and adjacent to helix alpha4 conferred defects in Spx-activated transcription but not Spx-dependent repression. Electrophoretic mobility-shift assays showed alphaCTD interaction with trxB promoter DNA, but addition of Spx generated a supershifted complex that was disrupted in the presence of reductant (DTT). Interaction of alphaCTD/Spx complex with promoter DNA required the cis-acting elements -45AGCA-42 and -34AGCG-31 of the trxB promoter. The Spx(G52R) mutant, defective in alphaCTD binding, did not interact with the alphaCTD-trxB complex. Spx(R60E) not only failed to complex with alphaCTD-trxB, but also disrupted alphaCTD-trxB DNA interaction.The results show that Spx and alphaCTD form a complex that recognizes the promoter DNA of an Spx-controlled gene. A conformational change during oxidation of Spx to the disulfide form likely alters the structure of Spx alpha helix alpha4, which contains residues that function in transcriptional activation and alphaCTD/Spx-promoter interaction. The results suggest that one of these residues, R60 of the alpha4 region of oxidized Spx, functions in alphaCTD/Spx-promoter contact but not in alphaCTD interaction
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