Cell
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Control and treatment of chronic pain remain major clinical challenges. Progress may be facilitated by a greater understanding of the mechanisms underlying pain processing. ⋯ Mice lacking DREAM had elevated levels of prodynorphin mRNA and dynorphin A peptides in the spinal cord, and the reduction of pain behaviors in dream(-/-) mice was mediated through dynorphin-selective kappa (kappa)-opiate receptors. Thus, DREAM appears to be a critical transcriptional repressor in pain processing.
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The hypothalamus plays a central role in the integrated control of feeding and energy homeostasis. We have identified two novel neuropeptides, both derived from the same precursor by proteolytic processing, that bind and activate two closely related (previously) orphan G protein-coupled receptors. These peptides, termed orexin-A and -B, have no significant structural similarities to known families of regulatory peptides. prepro-orexin mRNA and immunoreactive orexin-A are localized in neurons within and around the lateral and posterior hypothalamus in the adult rat brain. When administered centrally to rats, these peptides stimulate food consumption. prepro-orexin mRNA level is up-regulated upon fasting, suggesting a physiological role for the peptides as mediators in the central feedback mechanism that regulates feeding behavior.
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Thymocytes from mice congenitally deficient for TCR alpha chain synthesis were examined for the status of their TCR beta chain genes, by DNA sequencing and by a novel technique that analyzes populations of gene rearrangements. TCR beta chain genes were predominantly productively rearranged, in contrast with the statistical prediction for a quasi-random rearrangement process. ⋯ Moreover, the beta chain gene rearrangements in TCR alpha-/-mice are typical of those found in the thymus and periphery of normal mice. Thus, the extent of junctional diversity is a property of TCR genes that is imposed prior to selection on the mature alpha beta TCR.