Pre-hypertension (pre-HT) (Blood Pressure (BP) ≥120/80mmHg to ≤ 140/90mmHg) increases the risk of developing hypertension (HT). BP reductions following acute exercise are known as post exercise hypotension (PEH). BP and perhaps PEH shows a daily circadian rhythm. Purpose: To compare the magnitude of PEH after morning and evening aerobic exercise in adults with pre-HT. Hypothesis: The magnitude of PEH will be larger after evening versus morning exercise. Participants: Pre-HT men and women 50-65 years old. Study Design: Participants engaged in cycling exercise (60% VO2max) on two occasions: 1.5 and 11 hours following waking. Cardiovascular function was assessed for 30 minutes pre and one hour post exercise. Results: 1) Systolic PEH responses affected by TOD differed by gender. 2) Baseline Heart Rate Variability and its response to exercise differed gender but not TOD. The inconsistent significant gender and TOD differences of PEH and its mechanisms suggest that this group.

Cytokinins are plant hormones that affect the primary growth of shoots and roots. Application of the cytokinin N6-benzylaminopurine (BAP) to the shoot apical meristem of <i>Arabidopsis thaliana Landsberg erecta </i>(L.) Heynh induces aberrant flower development and a significant genetic response, and some of these phenotypes and expression patterns were carried to the next generation. Analysis of altered transcript levels with Affymetrix GeneChips® indicated significant changes in transcript levels of genes associated with shoot meristem activity, circadian rhythms, cytokinin metabolism, two-component systems, stress and defense responses, auxin regulation, ethylene and salicylic acid biosynthesis, and signal transduction. Specific genes were also mined from the data as potentially responsible for the BAP-induced aberrant floral phenotypes, increased floral organ number, buds in axils of sepals, and mosaic floral organs. Of particular note was a decrease in the transcript levels of CLAVATA1 (CLV1), a gene encoding a receptor kinase involved in organ differentiation and maintenance of shoot and floral meristems. Time course analysis by RT-PCR showed a decline and subsequent recovery of transcript levels of CLV1 and a coincident increase in WUSCHEL (WUS) transcript, consistent with the known suppression of WUS by CLV. WUS encodes a homeodomain protein associated with shoot meristem proliferation. The temporal coincidence of an increased floral organ phenotype with changes in transcript levels of CLV1 and WUS suggests that cytokinins regulate flower development by affecting the activity of genes controlling shoot meristem activity. Aberrant floral phenotypes in subsequent non-treated generations suggest epigenetic inheritance of some BAP-altered transcript patterns. Repressed expression of the majority of significant genes in the untreated T1 population suggests a mechanism of gene silencing, such as methylation, was involved in this epigenetic inheritance. Also, transcript levels of time-keeping genes, including CIRCADIAN CLOCK ASSOCIATED 1 / ELONGATED HYPOCOTYL, and associated genes with oscillating expression patterns, such as COLD-RESPONSIVE, were affected by BAP in treated plants and the subsequent generation, suggesting the capacity of cytokinins to affect the phase of the circadian clock. Hormonal regulation of heritably altered diurnal periodicity and environmental responses may provide a developmental and, therefore, evolutionary advantage to plants.

Cytokinins are plant hormones that affect the primary growth of shoots and roots. Application of the cytokinin N6-benzylaminopurine (BAP) to the shoot apical meristem of <i>Arabidopsis thaliana Landsberg erecta </i>(L.) Heynh induces aberrant flower development and a significant genetic response, and some of these phenotypes and expression patterns were carried to the next generation. Analysis of altered transcript levels with Affymetrix GeneChips® indicated significant changes in transcript levels of genes associated with shoot meristem activity, circadian rhythms, cytokinin metabolism, two-component systems, stress and defense responses, auxin regulation, ethylene and salicylic acid biosynthesis, and signal transduction. Specific genes were also mined from the data as potentially responsible for the BAP-induced aberrant floral phenotypes, increased floral organ number, buds in axils of sepals, and mosaic floral organs. Of particular note was a decrease in the transcript levels of CLAVATA1 (CLV1), a gene encoding a receptor kinase involved in organ differentiation and maintenance of shoot and floral meristems. Time course analysis by RT-PCR showed a decline and subsequent recovery of transcript levels of CLV1 and a coincident increase in WUSCHEL (WUS) transcript, consistent with the known suppression of WUS by CLV. WUS encodes a homeodomain protein associated with shoot meristem proliferation. The temporal coincidence of an increased floral organ phenotype with changes in transcript levels of CLV1 and WUS suggests that cytokinins regulate flower development by affecting the activity of genes controlling shoot meristem activity. Aberrant floral phenotypes in subsequent non-treated generations suggest epigenetic inheritance of some BAP-altered transcript patterns. Repressed expression of the majority of significant genes in the untreated T1 population suggests a mechanism of gene silencing, such as methylation, was involved in this epigenetic inheritance. Also, transcript levels of time-keeping genes, including CIRCADIAN CLOCK ASSOCIATED 1 / ELONGATED HYPOCOTYL, and associated genes with oscillating expression patterns, such as COLD-RESPONSIVE, were affected by BAP in treated plants and the subsequent generation, suggesting the capacity of cytokinins to affect the phase of the circadian clock. Hormonal regulation of heritably altered diurnal periodicity and environmental responses may provide a developmental and, therefore, evolutionary advantage to plants.

The liver maintains energy substrate homeostasis by synchronizing circadian or diurnal expression of metabolic genes with the feeding/fasting state. The activities of hepatic de novo lipogenic gene products peak during feeding, converting carbohydrates into fats that provide vital energy sources for peripheral tissues. Conversely, deregulated hepatic lipid synthesis leads to systemic metabolic dysfunction, establishing the importance of temporal regulation of fat synthesis/usage in metabolic homeostasis. Pharmacological activation of peroxisome proliferator-activated receptor \(\delta / \beta (PPAR \delta / \beta)\)improves glucose handling and systemic insulin sensitivity. However, the mechanisms of hepatic \(PPAR\delta\) actions and the molecular pathways through which it is able to modulate global metabolic homeostasis remain unclear. Here we show that hepatic \(PPAR\delta\) controls the diurnal expression of lipogenic genes in the dark/feeding cycle. Adenovirus mediated liver restricted activation of \(PPAR\delta\) promotes glucose utilization in the liver and fat utilization in the muscle. Liver specific deletion of either \(PPAR\delta\) or the \(PPAR\delta\)-regulated lipogenic gene acetyl-CoA carboxylase 1 (ACC1) reduces muscle fatty acid uptake. Unbiased metabolite profiling identifies 1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine (SOPC) as a serum lipid derived from the hepatic \(PPAR\delta\)-ACC1 activity that reduces postprandial lipid levels and increases muscle fatty acid uptake. These findings reveal a regulatory mechanism that coordinates lipid synthesis and utilization in the liver-muscle axis, providing mechanistic insights into the hepatic regulation of systemic energy substrates homeostasis.

No description available.

The circadian system provides animals with a means to adapt internal physiology to the constantly changing environmental stimuli that exists on a rotating planet. Light information is translated into molecular timing mechanisms within individual pacemaker cells of the mammalian hypothalamic suprachiasmatic nucleus (SCN) via transcriptionaltranslational feedback loops. Humoral and neural outputs from this master clock result in circadian rhythms of physiology and behavior. The hierarchy of the circadian system involves SCN synchronization of cellular clocks within peripheral tissues so that differential transcriptional profiles in individual organs reflect their specific function. The first step to investigating equine circadian regulation was to identify and isolate the core components of the molecular clock in the horse. Successful isolation and sequencing of equine Bmal1, Per2, Cry1 and Clock cDNAs revealed high sequence homology with their human counterparts. Real Time RT-PCR assays were subsequently designed to quantitatively assess clock gene expression in equine peripheral tissues. Synchronization of equine fibroblasts revealed temporal profiles of clock gene expression identical to those of the SCN and peripheral tissues of other species. However, while clock gene expression varies over time in equine adipose tissue, there was no observable oscillation of clock gene transcripts in equine blood. Spurred by recent reports of immune-circadian interactions, this novel finding prompted an investigation of clock gene expression in equine blood during a systemic inflammatory response. The results demonstrated that acute inflammation upregulates Per2 and Bmal1 in equine blood. Subsequent experiments identified neutrophils as the source of this upregulation and highlighted exciting new immunecircadian interplay during an innate immune response. Finally, the effect of a 6-h phase advance of the light/dark cycle, mimicking an easterly transmeridian journey, on circadian melatonin and core body temperature rhythms was investigated. In contrast to the gradual adaptation observed in other species, these markers of equine circadian phase adapt immediately to a time zone transition. Combined, the results of these experiments highlight important interspecies differences in circadian regulation with practical implications regarding the potential impact of jet lag on equine athletes. Furthermore, the results underline the relevance of chronobiological investigation in a large mammalian species such as the horse.

Thesis (Ph. D.)--University of Washington, 1989. / Vita. Includes bibliographical references (leaves [62]-66).

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.

The physiological and behavioral functions of the body are coordinated into daily patterns that are synchronized with the earth's light/dark cycles. This patterning of function is referred to as circadian rhythms. A central pacemaker located in suprachiasmatic nucleus of the brain serves to coordinate the body's rhythms with the light/dark cycle. Disturbances in normal circadian rhythm have been shown to increase the risk of certain types of cancer, including breast cancer. This effect is so significant that the World Health Organization has recently classified shift work as a probable carcinogen. One effect of alteration in the light/dark cycle such as that experienced by shift workers is a change in the production of the pineal hormone melatonin (N-acetyl-5-methoxytryptamine). Secretion of melatonin is regulated by the suprachiasmatic nucleus. Melatonin has a wide variety of functions including physiological regulation of sleep, modulation of the immune system and antioxidant action. Recent studies have determined that melatonin has oncostatic actions in a variety of cancers, including breast, prostate and endometrial cancer. Thus, this thesis explores the effects of melatonin on clock gene expression and growth of a mouse mammary tumor cell line, EMT6. I hypothesized that growth inhibitory actions of melatonin involve alteration in clock gene expression, induction of apoptosis and cell cycle arrest. Thus, this thesis investigates the modulatory effects of melatonin on clock genes, cell cycle parameters and apoptosis. Western blot analysis and immunocytochemistry confirmed expression of melatonin receptors in the EMT6 cell line. I investigated the circadian rhythm of EMT6 cells by measuring the clock gene expression pattern over a 24 hour period. I found a significant rhythm in Per1 and Per2 transcripts. Expression of estrogen and progesterone receptors was measured as they are putative clock controlled genes involved in the development of breast cancer. The results showed significant rhythm in Per1 (p=0.05), Per2 (p=0.03) and estrogen receptors ERalpha (p=0.001) and ERbeta (p=0.028). Peak expression for Period genes and ERalpha is found at 16 hrs and 20 hrs after serum shock, respectively. Peak expression for ERbeta is found at 24 hours after serum shock. Other steroid hormone receptors such as progesterone receptors PRB and PRA+B were not rhythmic. Treatment with melatonin in a concentration range from 10µM to 1nM inhibited growth in the cells. The antiproliferative effect of melatonin was dose and time dependent. At the end of 48 hours, melatonin at a concentration of 10-7 M induced apoptosis in EMT6 cells as indicated by caspase-3 immunocytochemistry. Furthermore, this same treatment caused an upregulation of the clock gene and putative tumor suppressor gene, Per2. These studies provide evidence that melatonin alters growth of EMT6 cells by inducing caspase-3 and apoptosis, which may be regulated through induction of Per2. Thus, disturbance in rhythmic secretion of melatonin may promote tumor progression in breast cancer.

Subterranean rodents are interesting model group for studying of the circadian timing system due to their cryptic lifestyle and challenging living conditions. The filed data indicate that the locomotor activity of the silvery mole-rat (Heliophobius argenteocinereus) is influenced by temperature cycle, but the confirmation in laboratory study was to date missing.