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Pharmacological validation of candidate causal sleep genes identified in an N2 cross.Despite the substantial impact of sleep disturbances on human health and the many years of study dedicated to understanding sleep pathologies, the underlying genetic mechanisms that govern sleep and wake largely remain unknown. Recently, the authors completed large-scale genetic and gene expression analyses in a segregating inbred mouse cross and identified candidate causal genes that regulate the mammalian sleep-wake cycle, across multiple traits including total sleep time, amounts of rapid eye ...201122091728
toll-like receptor 4 is a regulator of monocyte and electroencephalographic responses to sleep loss.study objectives: sleep loss triggers changes in inflammatory signaling pathways in the brain and periphery. the mechanisms that underlie these changes are ill-defined. the toll-like receptor 4 (tlr4) activates inflammatory signaling cascades in response to endogenous and pathogen-associated ligands known to be elevated in association with sleep loss. tlr4 is therefore a possible mediator of some of the inflammation-related effects of sleep loss. here we describe the baseline electroencephalogra ...201121966065
circadian control of mouse heart rate and blood pressure by the suprachiasmatic nuclei: behavioral effects are more significant than direct outputs.diurnal variations in the incidence of events such as heart attack and stroke suggest a role for circadian rhythms in the etiology of cardiovascular disease. the aim of this study was to assess the influence of the suprachiasmatic nucleus (scn) circadian clock on cardiovascular function.201020339544
specificity of direct transition from wake to rem sleep in orexin/ataxin-3 transgenic narcoleptic mice.to create operational criteria for polygraphic assessments of direct transitions from wake to rem sleep (drem), as a murine analog of human cataplexy, we have analyzed drem episodes in congenic lines of orexin/ataxin-3 transgenic [tg] mice and wild-type littermates. the sleep stage of each 10-second epoch was visually scored using our standard criteria. specificity of drem for narcoleptic tg mice and sensitivity to detect drem was evaluated using different drem criteria. we found that drem trans ...200919416673
the physiological role of orexins.orexins/hypocretins are recently discovered neuropeptides synthetized mainly by neurons located in the posterolateral hypothalamus. hypocretin-1 and -2 are the same peptides as orexin-a and orexin-b. orexin a is a 33 amino acid peptide with n-terminal pyroglutamyl residue and two intrachain disulphide bonds. orexin b is a linear peptide of 28 amino acids. these two peptides are potent agonists at both the orexin-1 (oxr1) and orexin-2 (oxr2) receptors. orexin-a is selective ligand for oxr1 and ox ...200516135995
dna-binding specificity and trans-activating potential of the leukemia-associated e2a-hepatic leukemia factor fusion protein.hybrid transcription factors, resulting from gene fusions in the wake of chromosomal translocations, have been implicated in leukemogenesis, but their precise contributions to oncogenic conversion remain unclear. the e2a-hlf fusion gene, formed by a t(17;19)(q22;p13) in childhood pro-b-cell acute lymphoid leukemia, encodes a hybrid protein that contains the trans-activation domain of e2a (e12/e47) linked to the bzip dna-binding and dimerization domain of hepatic leukemia factor (hlf). here we re ...19948164688
when clocks go bad: neurobehavioural consequences of disrupted circadian timing.progress in unravelling the cellular and molecular basis of mammalian circadian regulation over the past decade has provided us with new avenues through which we can explore central nervous system disease. deteriorations in measurable circadian output parameters, such as sleep/wake deficits and dysregulation of circulating hormone levels, are common features of most central nervous system disorders. at the core of the mammalian circadian system is a complex of molecular oscillations within the h ...200818516223
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