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BACKGROUND GPRC6A is a widely expressed orphan G-protein coupled receptor that senses extracellular amino acids, osteocalcin and divalent cations in vitro. The physiological functions of GPRC6A are unknown. METHODS/PRINCIPAL FINDINGS In this study, we created and characterized the phenotype of GPRC6A(-/-) mice. We observed complex metabolic abnormalities(More)
The C family G-protein-coupled receptors contain members that sense amino acid and extracellular cations, of which calcium-sensing receptor (CASR) is the prototypic extracellular calcium-sensing receptor. Some cells, such as osteoblasts in bone, retain responsiveness to extracellular calcium in CASR-deficient mice, consistent with the existence of another(More)
Flap endonuclease-1 (FEN1) is a key enzyme involved in base excision repair (BER), a primary pathway utilized by mammalian cells to repair DNA damage. Sensitization to DNA damaging agents is a potential method for the improvement of the therapeutic window of traditional chemotherapeutics. In this paper, we describe the identification and SAR of a series of(More)
The NF-kappaB pathway plays a critical role in regulating cellular processes such as immune responses, stress responses, apoptosis, proliferation and differentiation, whereas dysfunction of this pathway has been associated with numerous cancer and immune disorders. We have applied our Random Activation of Gene Expression technology to an NF-kappaB reporter(More)
BACKGROUND The prevalence and nature of sleep disorders in primary care has not been widely studied. As part of a survey conducted in 5 family practice offices in North Carolina, we screened adult patients for sleep syndromes and sought to ascertain which demographic status and health status were associated with these disorders. METHODS We approached 2963(More)
Analogues of the natural product noscapine were synthesized and their potential as antitumor agents evaluated. The discovery of a novel regioselective O-demethylation facilitated the synthesis of the potent aniline 6, which arrests mammalian cells in the G2/M phase of the cell cycle at 0.1 microM and also affects tubulin polymerization. Aniline 6 is orally(More)
Because there is insufficient cellular energy for organisms to perform their functions at the same constant rate and at the same time, all biologic processes show rhythmicity, each with its own unique frequency, amplitude, and phase. Optimal sleep and wakefulness requires proper timing and alignment of desired sleep-wake schedules and circadian(More)
Sleep disturbances are common among older adults. The elderly population reports more symptoms associated with poor sleep initiation and maintenance and increased daytime napping. Sleep problems may be caused by various factors, including medication use, medical and psychiatric illnesses, and primary sleep disorders. The consequences of poor sleep quality(More)
OBJECTIVE Sleep-related material in medical textbooks may be the only method by which physicians educate themselves about sleep. In the last decade significant progress in sleep research has been made, but how textbooks in relevant fields reflect it has not been examined. Our purpose was to review and compare (2005 with 1998) sleep content in representative(More)
In this article, the combined effects of aging and obesity on the respiratory system are examined. Following a concise epidemiologic overview of the prevalence of obesity among older adults, the occurrence of prospective, often variable, health consequences related to this trend are considered as well as the observed effects of the association of both aging(More)