Abstract Frequent transmeridian flights or predominant work at night can increase cancer risk. Altered circadian rhythms also predict for poor survival in patients, whereas physical destruction of the suprachiasmatic nuclei (SCN), hypothalamic pacemaker, accelerates tumor growth mice. Here we tested effect functional disruption system on progression a novel experimental model chronic jet lag. B6D2F1 mice were synchronized with 12 hours light and darkness underwent repeat 8-hour advances...

Recent evidence has emerged that peroxisome proliferator-activated receptor alpha (PPARalpha), which is largely involved in lipid metabolism, can play an important role connecting circadian biology and metabolism. In the present study, we investigated mechanisms by PPARalpha influences pacemakers acting central clock located suprachiasmatic nucleus peripheral oscillator of liver. We demonstrate plays a specific control because it required to maintain rhythm master gene brain muscle Arnt-like...

Mutations of clock genes can lead to diabetes and obesity. REV-ERBα, a nuclear receptor involved in the circadian clockwork, has been shown control lipid metabolism. To gain insight into role REV-ERBα energy homeostasis vivo, we explored daily metabolism carbohydrates lipids chow-fed, unfed, or high-fat-fed Rev-erbα−/− mice their wild-type littermates. Chow-fed displayed increased adiposity (2.5-fold) mild hyperglycemia (∼10%) without insulin resistance. Indirect calorimetry indicates that...

Daily synchronous rhythms of cell division at the tissue or organism level are observed in many species and suggest that circadian clock cycle oscillators coupled. For mammals, despite known mechanistic interactions, effect such coupling on progression, hence its biological relevance, is not understood. In particular, we do know how temporal organization single-cell produces this daily rhythm level. Here use multispectral imaging single live cells, computational methods, mathematical...

Abnormalities contributing to the pathogenesis of non-insulin-dependent diabetes mellitus include impaired beta cell function, peripheral insulin resistance, and increased hepatic glucose production. Glucocorticoids are diabetogenic hormones because they decrease uptake increase In addition, may directly inhibit release. To evaluate that possible role glucocorticoids in function independent their other effects, transgenic mice with an glucocorticoid sensitivity restricted cells were...

Most living organisms show circadian (∼24 h) rhythms in physiology and behavior. These oscillations are generated by endogenous clocks, present virtually all cells where they control key biological processes. Although gating of mitosis has been reported for many years some peripheral tissues, the underlying molecular mechanisms have remained poorly understood. Here we that cell cycle inhibitor p21WAF1/CIP1 is rhythmically expressed mouse organs. This rhythmic pattern mRNA protein expression...

Circadian clocks are time-keeping systems found in most organisms. In zebrafish, expression of the clock gene Period3 ( Per3 ) oscillates throughout embryogenesis central nervous system and retina. rhythmic was free-running reset by light but not developmental delays caused low temperature. The time fertilization had no effect on expression. messenger RNA accumulates rhythmically oocytes persists embryos. Our results establish that circadian functions during early zebrafish. Inheritance...

Rev-erbα [NR1D1], a member of the nuclear receptor superfamily, is an orphan that constitutively represses gene transcription. has been shown to play role in myocyte differentiation and be induced during adipogenesis. Furthermore, regulator lipoprotein metabolism. It was recently messenger RNA (mRNA) levels oscillate diurnally rat liver. Here, we report circadian rhythm liver maintained primary cultures hepatocytes. Because glucocorticoids have regulate other transcription factors with...

Rev-erbalpha is a ubiquitously expressed orphan nuclear receptor which functions as constitutive transcriptional repressor and in vertebrates according to robust circadian rhythm. We report here that two mRNA isoforms, namely Rev-erbalpha1 2, are generated through alternative promoter usage both show expression pattern an vitro system using serum-shocked fibroblasts. Both regions P1 (Rev-erbalpha1) P2 (Rev-erbalpha2) contain several E-box DNA sequences function response elements for the core...

Human estrogen receptors α (ERα) and β (ERβ) are ligand-inducible transcription factors that highly homologous in their central DNA-binding carboxyl-terminal ligand-binding domains. In contrast, there is very little conservation between ERα ERβ the amino-terminal domain. Using different human cell lines, we show wild-type transcriptional activity lower or similar to of ERα, depending on type. Deletion domain both ER subtypes resulted no a decrease compared with suggesting contains weaker...

Glucocorticoids inhibit NF-κB signaling by interfering with the transcription factor RelA. Previous studies have identified DNA-binding domain (DBD) in glucocorticoid receptor (GR) as major region responsible for this repressive activity. Using GR mutants chimeric DBDs function was found to be located C-terminal zinc finger. As predicted from these results mineralocorticoid that contains a finger identical of also able repress RelA-dependent transcription. Mutation conserved arginine or...

Abstract Circadian disruption accelerates cancer progression, whereas circadian reinforcement could halt it. Mice with P03 pancreatic adenocarcinoma (n = 77) were synchronized and fed ad libitum (AL) or meal timing (MT) from Zeitgeber time (ZT) 2 to ZT6 normal fat diet. Tumor gene expression profiling was determined DNA microarrays at endogenous (CT) 4 CT16. mRNA patterns for clock genes Rev-erbα, Per2, Bmal1, cellular stress Hspa8 Cirbp, cyclin A2 Ccna2 in liver tumor. The 24-hour...

The circadian timing system coordinates many aspects of mammalian physiology and behavior in synchrony with the external light/dark cycle. These rhythms are driven by endogenous molecular clocks present most body cells. Many clock outputs transcriptional regulators, suggesting that genes primarily control through indirect pathways. Here, we show Krüppel-like factor 10 (KLF10) displays a robust expression pattern wild-type mouse liver but not clock-deficient Bmal1 knockout mice. Consistently,...

Abstract Introduction In the emergency setting, focused cardiac ultrasound has become a fundamental tool for diagnostic, initial treatment and triage decisions. A new ultra-miniaturized pocket device (PUD) may be suited to this specific setting. Therefore, we aimed compare diagnostic ability of an (Vscan™, GE Healthcare, Wauwatosa, WI) conventional high-quality echocardiography system (Vivid S5™, Healthcare) ultrasonography in patients admitted department. Methods During 4 months, our...

Genes under a 24-h regulation period may represent drug targets relevant to diseases involving circadian dysfunctions. As testing model of the clock system, we have used synchronized rat fibroblasts that are known express at least six genes in fashion. We determined expression patterns 9957 transcripts every 4 h over total 76 using high density oligonucleotide microarrays. The spectral analysis our mRNA profiling data indicated ∼2% (85 genes) all expressed followed robust pattern. confirmed...

Circadian timing of anticancer medications has improved treatment tolerability and efficacy several fold, yet with intersubject variability. Using three C57BL/6-based mouse strains both sexes, we identified chronotoxicity classes distinct circadian toxicity patterns irinotecan, a topoisomerase I inhibitor active against colorectal cancer. Liver colon 24-hour expression clock genes Rev-erbα Bmal1 best discriminated these classes, among 27 transcriptional time series, according to sparse...

Central and peripheral mammalian circadian clocks regulate a variety of behavioral physiological processes through the rhythmic transcription hundreds clock-controlled genes. The expression many transcriptional regulators suggests that major part this gene network is indirectly regulated by clock Here we show basic helix-loop-helix repressor Stra13 rhythmically expressed in mouse organs. mediated response element recognized CLOCK-BMAL1 heterodimer located proximal promoter region....